US20110142919A1 - Cytotoxic T-Lymphocyte-Inducing Immunogens for Prevention, Treatment and Diagnosis of Cancer - Google Patents
Cytotoxic T-Lymphocyte-Inducing Immunogens for Prevention, Treatment and Diagnosis of Cancer Download PDFInfo
- Publication number
- US20110142919A1 US20110142919A1 US13/030,563 US201113030563A US2011142919A1 US 20110142919 A1 US20110142919 A1 US 20110142919A1 US 201113030563 A US201113030563 A US 201113030563A US 2011142919 A1 US2011142919 A1 US 2011142919A1
- Authority
- US
- United States
- Prior art keywords
- protein
- amino acid
- peptide
- peptides
- seq
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Abandoned
Links
- 206010028980 Neoplasm Diseases 0.000 title claims abstract description 73
- 201000011510 cancer Diseases 0.000 title claims abstract description 40
- 238000011282 treatment Methods 0.000 title abstract description 25
- 230000002265 prevention Effects 0.000 title abstract description 7
- 238000003745 diagnosis Methods 0.000 title abstract description 4
- 231100000433 cytotoxic Toxicity 0.000 title 1
- 230000001472 cytotoxic effect Effects 0.000 title 1
- 108090000765 processed proteins & peptides Proteins 0.000 claims abstract description 341
- 102000004196 processed proteins & peptides Human genes 0.000 claims abstract description 232
- 229920001184 polypeptide Polymers 0.000 claims abstract description 104
- 238000000034 method Methods 0.000 claims abstract description 79
- 230000004044 response Effects 0.000 claims abstract description 42
- 239000000203 mixture Substances 0.000 claims abstract description 28
- 206010033128 Ovarian cancer Diseases 0.000 claims abstract description 23
- 201000009030 Carcinoma Diseases 0.000 claims abstract description 8
- 150000001413 amino acids Chemical class 0.000 claims description 55
- 125000003275 alpha amino acid group Chemical group 0.000 claims description 35
- 210000004881 tumor cell Anatomy 0.000 claims description 33
- 102000004127 Cytokines Human genes 0.000 claims description 17
- 108090000695 Cytokines Proteins 0.000 claims description 17
- 238000006467 substitution reaction Methods 0.000 claims description 15
- 239000002502 liposome Substances 0.000 claims description 11
- 239000002671 adjuvant Substances 0.000 claims description 10
- 108010017213 Granulocyte-Macrophage Colony-Stimulating Factor Proteins 0.000 claims description 6
- 239000002245 particle Substances 0.000 claims description 6
- 230000002209 hydrophobic effect Effects 0.000 claims description 5
- 150000003904 phospholipids Chemical class 0.000 claims description 3
- 239000003981 vehicle Substances 0.000 claims description 3
- 229940037003 alum Drugs 0.000 claims description 2
- WNROFYMDJYEPJX-UHFFFAOYSA-K aluminium hydroxide Chemical compound [OH-].[OH-].[OH-].[Al+3] WNROFYMDJYEPJX-UHFFFAOYSA-K 0.000 claims description 2
- ILRRQNADMUWWFW-UHFFFAOYSA-K aluminium phosphate Chemical compound O1[Al]2OP1(=O)O2 ILRRQNADMUWWFW-UHFFFAOYSA-K 0.000 claims description 2
- DIZPMCHEQGEION-UHFFFAOYSA-H aluminium sulfate (anhydrous) Chemical compound [Al+3].[Al+3].[O-]S([O-])(=O)=O.[O-]S([O-])(=O)=O.[O-]S([O-])(=O)=O DIZPMCHEQGEION-UHFFFAOYSA-H 0.000 claims description 2
- 239000006185 dispersion Substances 0.000 claims description 2
- 239000000839 emulsion Substances 0.000 claims description 2
- 239000006260 foam Substances 0.000 claims description 2
- 239000013546 insoluble monolayer Substances 0.000 claims description 2
- 239000010410 layer Substances 0.000 claims description 2
- 239000004973 liquid crystal related substance Substances 0.000 claims description 2
- 239000001397 quillaja saponaria molina bark Substances 0.000 claims description 2
- 229930182490 saponin Natural products 0.000 claims description 2
- 150000007949 saponins Chemical class 0.000 claims description 2
- 102000004457 Granulocyte-Macrophage Colony-Stimulating Factor Human genes 0.000 claims 1
- 102000017578 LAG3 Human genes 0.000 claims 1
- 101150030213 Lag3 gene Proteins 0.000 claims 1
- 238000012217 deletion Methods 0.000 claims 1
- 230000037430 deletion Effects 0.000 claims 1
- 230000003308 immunostimulating effect Effects 0.000 claims 1
- 239000000693 micelle Substances 0.000 claims 1
- 102000040430 polynucleotide Human genes 0.000 abstract description 28
- 108091033319 polynucleotide Proteins 0.000 abstract description 28
- 239000002157 polynucleotide Substances 0.000 abstract description 28
- 108090000623 proteins and genes Proteins 0.000 description 297
- 102000004169 proteins and genes Human genes 0.000 description 274
- 235000018102 proteins Nutrition 0.000 description 270
- 239000002243 precursor Substances 0.000 description 175
- 210000001151 cytotoxic T lymphocyte Anatomy 0.000 description 124
- 210000004027 cell Anatomy 0.000 description 103
- 230000002163 immunogen Effects 0.000 description 63
- 235000001014 amino acid Nutrition 0.000 description 50
- 229940024606 amino acid Drugs 0.000 description 48
- 241000282414 Homo sapiens Species 0.000 description 44
- 102000008949 Histocompatibility Antigens Class I Human genes 0.000 description 38
- 108010088652 Histocompatibility Antigens Class I Proteins 0.000 description 38
- 108010029485 Protein Isoforms Proteins 0.000 description 38
- 102000001708 Protein Isoforms Human genes 0.000 description 38
- 102000005962 receptors Human genes 0.000 description 33
- 108020003175 receptors Proteins 0.000 description 33
- 210000001744 T-lymphocyte Anatomy 0.000 description 29
- 108010074032 HLA-A2 Antigen Proteins 0.000 description 27
- 239000012634 fragment Substances 0.000 description 27
- 102000025850 HLA-A2 Antigen Human genes 0.000 description 26
- 102100023921 Serine/threonine-protein kinase ATR Human genes 0.000 description 26
- 239000000427 antigen Substances 0.000 description 26
- 108091007433 antigens Proteins 0.000 description 26
- 102000036639 antigens Human genes 0.000 description 26
- 210000000612 antigen-presenting cell Anatomy 0.000 description 24
- 230000027455 binding Effects 0.000 description 24
- 102000015636 Oligopeptides Human genes 0.000 description 23
- 108010038807 Oligopeptides Proteins 0.000 description 23
- 238000000338 in vitro Methods 0.000 description 23
- 230000001105 regulatory effect Effects 0.000 description 23
- 108010035452 HLA-A1 Antigen Proteins 0.000 description 21
- 108020004414 DNA Proteins 0.000 description 20
- 102100037978 InaD-like protein Human genes 0.000 description 20
- 102100022623 Hepatocyte growth factor receptor Human genes 0.000 description 19
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 18
- 108700018351 Major Histocompatibility Complex Proteins 0.000 description 17
- 230000001419 dependent effect Effects 0.000 description 17
- 210000004698 lymphocyte Anatomy 0.000 description 17
- 230000020382 suppression by virus of host antigen processing and presentation of peptide antigen via MHC class I Effects 0.000 description 17
- 101710088275 InaD-like protein Proteins 0.000 description 16
- 102100039648 Lactadherin Human genes 0.000 description 16
- 108010022579 ATP dependent 26S protease Proteins 0.000 description 14
- 108091006112 ATPases Proteins 0.000 description 14
- 102000057290 Adenosine Triphosphatases Human genes 0.000 description 14
- 108090000461 Aurora Kinase A Proteins 0.000 description 14
- 108090000749 Aurora kinase B Proteins 0.000 description 14
- 102100031702 Endoplasmic reticulum membrane sensor NFE2L1 Human genes 0.000 description 14
- 230000000890 antigenic effect Effects 0.000 description 14
- 102100026126 Proline-tRNA ligase Human genes 0.000 description 13
- 102100031298 Proteasome activator complex subunit 3 Human genes 0.000 description 13
- 102100030402 Transcription elongation factor SPT5 Human genes 0.000 description 13
- 230000000694 effects Effects 0.000 description 13
- 239000013598 vector Substances 0.000 description 13
- 108091000126 Dihydroorotase Proteins 0.000 description 12
- 102100025894 Glomulin Human genes 0.000 description 12
- 101710088083 Glomulin Proteins 0.000 description 12
- 108010036972 HLA-A11 Antigen Proteins 0.000 description 12
- 102100031775 Leptin receptor Human genes 0.000 description 12
- 102100021087 Regulator of nonsense transcripts 2 Human genes 0.000 description 12
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 12
- 239000012190 activator Substances 0.000 description 12
- 238000013459 approach Methods 0.000 description 12
- 230000001939 inductive effect Effects 0.000 description 12
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 11
- 125000000539 amino acid group Chemical class 0.000 description 11
- 108020004999 messenger RNA Proteins 0.000 description 11
- 230000002438 mitochondrial effect Effects 0.000 description 11
- 230000008569 process Effects 0.000 description 11
- 239000000047 product Substances 0.000 description 11
- 102100025339 ATP-dependent DNA helicase DDX11 Human genes 0.000 description 10
- 102100029949 Caprin-1 Human genes 0.000 description 10
- 102100031334 Elongation factor 2 Human genes 0.000 description 10
- 102100030540 Gap junction alpha-5 protein Human genes 0.000 description 10
- 101710191666 Lactadherin Proteins 0.000 description 10
- 108010077519 Peptide Elongation Factor 2 Proteins 0.000 description 10
- 108091000080 Phosphotransferase Proteins 0.000 description 10
- 101710103857 Proteasome activator complex subunit 3 Proteins 0.000 description 10
- 102100022093 Protocadherin Fat 2 Human genes 0.000 description 10
- 102100029938 Serine/threonine-protein kinase SMG1 Human genes 0.000 description 10
- 102100021170 Transcription initiation factor TFIID subunit 6 Human genes 0.000 description 10
- 101710104806 Transcription initiation factor TFIID subunit 6 Proteins 0.000 description 10
- 238000003556 assay Methods 0.000 description 10
- 210000003819 peripheral blood mononuclear cell Anatomy 0.000 description 10
- 102000020233 phosphotransferase Human genes 0.000 description 10
- 230000000638 stimulation Effects 0.000 description 10
- 229960005486 vaccine Drugs 0.000 description 10
- 206010006187 Breast cancer Diseases 0.000 description 9
- 208000026310 Breast neoplasm Diseases 0.000 description 9
- 101710072528 Caprin-1 Proteins 0.000 description 9
- 108091026890 Coding region Proteins 0.000 description 9
- 208000001333 Colorectal Neoplasms Diseases 0.000 description 9
- 101710157062 Endoplasmic reticulum membrane sensor NFE2L1 Proteins 0.000 description 9
- 108091008794 FGF receptors Proteins 0.000 description 9
- 108010041357 Integrin alpha3 Proteins 0.000 description 9
- 102100033421 Keratin, type I cytoskeletal 18 Human genes 0.000 description 9
- 206010058467 Lung neoplasm malignant Diseases 0.000 description 9
- 102400000977 Nuclear pore complex protein Nup98 Human genes 0.000 description 9
- 101800000051 Nuclear pore complex protein Nup98 Proteins 0.000 description 9
- 102100026168 P2Y purinoceptor 13 Human genes 0.000 description 9
- 102100029264 Protocadherin gamma-A12 Human genes 0.000 description 9
- 102100034585 Rap guanine nucleotide exchange factor 2 Human genes 0.000 description 9
- 108050004611 Rap guanine nucleotide exchange factor 2 Proteins 0.000 description 9
- 108090000873 Receptor Protein-Tyrosine Kinases Proteins 0.000 description 9
- 210000004443 dendritic cell Anatomy 0.000 description 9
- 239000013604 expression vector Substances 0.000 description 9
- 230000028993 immune response Effects 0.000 description 9
- 201000001441 melanoma Diseases 0.000 description 9
- 230000037361 pathway Effects 0.000 description 9
- 108050001315 26S Proteasome non-ATPase regulatory subunit 1 Proteins 0.000 description 8
- 102100040973 26S proteasome non-ATPase regulatory subunit 1 Human genes 0.000 description 8
- 102100021523 BPI fold-containing family A member 1 Human genes 0.000 description 8
- 102100023046 Band 4.1-like protein 3 Human genes 0.000 description 8
- 108050002669 Band 4.1-like protein 3 Proteins 0.000 description 8
- 102100035475 Blood vessel epicardial substance Human genes 0.000 description 8
- 206010009944 Colon cancer Diseases 0.000 description 8
- 102100034581 Dihydroorotase Human genes 0.000 description 8
- 102100039818 Frizzled-5 Human genes 0.000 description 8
- 101710140951 Frizzled-5 Proteins 0.000 description 8
- 102100028617 GRIP and coiled-coil domain-containing protein 2 Human genes 0.000 description 8
- 102100032510 Heat shock protein HSP 90-beta Human genes 0.000 description 8
- 108010024124 Histone Deacetylase 1 Proteins 0.000 description 8
- 102100039996 Histone deacetylase 1 Human genes 0.000 description 8
- 101000722210 Homo sapiens ATP-dependent DNA helicase DDX11 Proteins 0.000 description 8
- 101000899089 Homo sapiens BPI fold-containing family A member 1 Proteins 0.000 description 8
- 102100034845 KiSS-1 receptor Human genes 0.000 description 8
- 102100034865 Kinesin-like protein KIF13A Human genes 0.000 description 8
- 102100030477 Plectin Human genes 0.000 description 8
- 102100033428 Ras/Rap GTPase-activating protein SynGAP Human genes 0.000 description 8
- 101710199923 Ras/Rap GTPase-activating protein SynGAP Proteins 0.000 description 8
- 101710178061 Serine/threonine-protein kinase ATR Proteins 0.000 description 8
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 8
- 101710028540 UPF2 Proteins 0.000 description 8
- 102100020914 Zinc finger and SCAN domain-containing protein 20 Human genes 0.000 description 8
- 201000010989 colorectal carcinoma Diseases 0.000 description 8
- 201000010099 disease Diseases 0.000 description 8
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 8
- 238000001727 in vivo Methods 0.000 description 8
- 108010019813 leptin receptors Proteins 0.000 description 8
- 239000000463 material Substances 0.000 description 8
- 230000001404 mediated effect Effects 0.000 description 8
- 102100030146 Epithelial membrane protein 3 Human genes 0.000 description 7
- 102000013366 Filamin Human genes 0.000 description 7
- 108060002900 Filamin Proteins 0.000 description 7
- 102100022627 Fructose-2,6-bisphosphatase Human genes 0.000 description 7
- 108010002350 Interleukin-2 Proteins 0.000 description 7
- 102100027251 Melanoma-associated antigen D2 Human genes 0.000 description 7
- 102100023181 Neurogenic locus notch homolog protein 1 Human genes 0.000 description 7
- 108091028043 Nucleic acid sequence Proteins 0.000 description 7
- 206010061535 Ovarian neoplasm Diseases 0.000 description 7
- 102100024952 Protein CBFA2T1 Human genes 0.000 description 7
- 102100038150 RNA-binding protein 6 Human genes 0.000 description 7
- 101710085356 Serine/threonine-protein kinase SMG1 Proteins 0.000 description 7
- 108050006838 Transcription elongation factor SPT5 Proteins 0.000 description 7
- 102000040945 Transcription factor Human genes 0.000 description 7
- 108091023040 Transcription factor Proteins 0.000 description 7
- 102100035222 Transcription initiation factor TFIID subunit 1 Human genes 0.000 description 7
- 108050004072 Transcription initiation factor TFIID subunit 1 Proteins 0.000 description 7
- 108090000848 Ubiquitin Proteins 0.000 description 7
- 102000044159 Ubiquitin Human genes 0.000 description 7
- 230000002068 genetic effect Effects 0.000 description 7
- 230000010005 growth-factor like effect Effects 0.000 description 7
- 210000004901 leucine-rich repeat Anatomy 0.000 description 7
- 238000003786 synthesis reaction Methods 0.000 description 7
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 7
- MTCFGRXMJLQNBG-REOHCLBHSA-N (2S)-2-Amino-3-hydroxypropansäure Chemical compound OC[C@H](N)C(O)=O MTCFGRXMJLQNBG-REOHCLBHSA-N 0.000 description 6
- 108010085238 Actins Proteins 0.000 description 6
- 102000007469 Actins Human genes 0.000 description 6
- 102100021886 Activin receptor type-2A Human genes 0.000 description 6
- 101710174254 Blood vessel epicardial substance Proteins 0.000 description 6
- 102100033229 Centrosomal protein of 70 kDa Human genes 0.000 description 6
- 102100039193 Cullin-2 Human genes 0.000 description 6
- 101710094489 Cullin-2 Proteins 0.000 description 6
- 102100029145 DNA damage-inducible transcript 3 protein Human genes 0.000 description 6
- 102100021579 Enhancer of filamentation 1 Human genes 0.000 description 6
- 102100023600 Fibroblast growth factor receptor 2 Human genes 0.000 description 6
- 101710182389 Fibroblast growth factor receptor 2 Proteins 0.000 description 6
- 102100027988 GTP-binding protein Rhes Human genes 0.000 description 6
- 101710177922 Gap junction alpha-5 protein Proteins 0.000 description 6
- 108010015514 Glutamate-tRNA ligase Proteins 0.000 description 6
- 102100039620 Granulocyte-macrophage colony-stimulating factor Human genes 0.000 description 6
- 101001054793 Homo sapiens Importin subunit alpha-7 Proteins 0.000 description 6
- 101001091266 Homo sapiens Kinesin-like protein KIF13A Proteins 0.000 description 6
- 101001034314 Homo sapiens Lactadherin Proteins 0.000 description 6
- 101000988229 Homo sapiens Protocadherin gamma-A12 Proteins 0.000 description 6
- 101000702364 Homo sapiens Transcription elongation factor SPT5 Proteins 0.000 description 6
- 102000004157 Hydrolases Human genes 0.000 description 6
- 108090000604 Hydrolases Proteins 0.000 description 6
- 102100027002 Importin subunit alpha-7 Human genes 0.000 description 6
- 108010022238 Integrin beta4 Proteins 0.000 description 6
- 102100027355 Interferon-induced protein with tetratricopeptide repeats 1 Human genes 0.000 description 6
- 101710166699 Interferon-induced protein with tetratricopeptide repeats 1 Proteins 0.000 description 6
- 102100025505 Intersectin-2 Human genes 0.000 description 6
- 108010076800 Kisspeptin-1 Receptors Proteins 0.000 description 6
- 102400000018 Lamin-A/C Human genes 0.000 description 6
- 102100031036 Leucine-rich repeat-containing G-protein coupled receptor 5 Human genes 0.000 description 6
- 102100032894 Liprin-alpha-2 Human genes 0.000 description 6
- 102000043136 MAP kinase family Human genes 0.000 description 6
- 108091054455 MAP kinase family Proteins 0.000 description 6
- 102100034771 Mediator of RNA polymerase II transcription subunit 23 Human genes 0.000 description 6
- 102100027255 Melanoma-associated antigen E2 Human genes 0.000 description 6
- 108060004795 Methyltransferase Proteins 0.000 description 6
- 102100033060 Mitogen-activated protein kinase kinase kinase 4 Human genes 0.000 description 6
- 102100034263 Mucin-2 Human genes 0.000 description 6
- 108010008705 Mucin-2 Proteins 0.000 description 6
- 102100030436 Nuclear autoantigen Sp-100 Human genes 0.000 description 6
- 101710118310 Nuclear autoantigen Sp-100 Proteins 0.000 description 6
- 102100037226 Nuclear receptor coactivator 2 Human genes 0.000 description 6
- 108090001144 Nuclear receptor coactivator 2 Proteins 0.000 description 6
- 108700026244 Open Reading Frames Proteins 0.000 description 6
- 101710192337 P2Y purinoceptor 13 Proteins 0.000 description 6
- 102000004160 Phosphoric Monoester Hydrolases Human genes 0.000 description 6
- 108090000608 Phosphoric Monoester Hydrolases Proteins 0.000 description 6
- 108010054050 Plectin Proteins 0.000 description 6
- 101710198637 Probable G-protein coupled receptor Proteins 0.000 description 6
- 102100029002 Prolactin-releasing peptide receptor Human genes 0.000 description 6
- 108700024163 Prolactin-releasing peptide receptors Proteins 0.000 description 6
- 206010060862 Prostate cancer Diseases 0.000 description 6
- 102100032420 Protein S100-A9 Human genes 0.000 description 6
- 108091008874 T cell receptors Proteins 0.000 description 6
- 102000016266 T-Cell Antigen Receptors Human genes 0.000 description 6
- 230000015572 biosynthetic process Effects 0.000 description 6
- 201000008275 breast carcinoma Diseases 0.000 description 6
- 102000005352 centromere protein F Human genes 0.000 description 6
- 108010031377 centromere protein F Proteins 0.000 description 6
- 210000000349 chromosome Anatomy 0.000 description 6
- 230000009089 cytolysis Effects 0.000 description 6
- 108010008486 gp100 Melanoma Antigen Proteins 0.000 description 6
- 102000007192 gp100 Melanoma Antigen Human genes 0.000 description 6
- 238000009169 immunotherapy Methods 0.000 description 6
- 108090000681 interleukin 20 Proteins 0.000 description 6
- 230000000670 limiting effect Effects 0.000 description 6
- 201000005296 lung carcinoma Diseases 0.000 description 6
- 239000012528 membrane Substances 0.000 description 6
- 210000004379 membrane Anatomy 0.000 description 6
- 201000001514 prostate carcinoma Diseases 0.000 description 6
- 239000000243 solution Substances 0.000 description 6
- 230000004936 stimulating effect Effects 0.000 description 6
- 230000035897 transcription Effects 0.000 description 6
- 238000013518 transcription Methods 0.000 description 6
- 102100032301 26S proteasome non-ATPase regulatory subunit 3 Human genes 0.000 description 5
- 101710091327 26S proteasome non-ATPase regulatory subunit 3 Proteins 0.000 description 5
- 102100027271 40S ribosomal protein SA Human genes 0.000 description 5
- 102100022406 60S ribosomal protein L10a Human genes 0.000 description 5
- 101710155230 60S ribosomal protein L10a Proteins 0.000 description 5
- 102100021247 BCL-6 corepressor Human genes 0.000 description 5
- 102000000905 Cadherin Human genes 0.000 description 5
- 108050007957 Cadherin Proteins 0.000 description 5
- 102000014914 Carrier Proteins Human genes 0.000 description 5
- 102100030972 Coatomer subunit beta Human genes 0.000 description 5
- 101710186199 Coatomer subunit beta Proteins 0.000 description 5
- 102100031635 Cytoplasmic dynein 1 heavy chain 1 Human genes 0.000 description 5
- 101710204897 Cytoplasmic dynein 1 heavy chain 1 Proteins 0.000 description 5
- 108090000626 DNA-directed RNA polymerases Proteins 0.000 description 5
- 102000004163 DNA-directed RNA polymerases Human genes 0.000 description 5
- 101710165788 Dynein heavy chain, cytoplasmic Proteins 0.000 description 5
- 102100026149 Fibroblast growth factor receptor-like 1 Human genes 0.000 description 5
- 101710084357 Fibroblast growth factor receptor-like 1 Proteins 0.000 description 5
- 108091006027 G proteins Proteins 0.000 description 5
- 102000030782 GTP binding Human genes 0.000 description 5
- 108091000058 GTP-Binding Proteins 0.000 description 5
- 101710163596 Heat shock protein HSP 90-beta Proteins 0.000 description 5
- 102100030483 Histatin-1 Human genes 0.000 description 5
- 101001057154 Homo sapiens Melanoma-associated antigen D2 Proteins 0.000 description 5
- 101000743264 Homo sapiens RNA-binding protein 6 Proteins 0.000 description 5
- 102100036398 Importin-13 Human genes 0.000 description 5
- 102100032819 Integrin alpha-3 Human genes 0.000 description 5
- 108050006944 Keratin, type I cytoskeletal 18 Proteins 0.000 description 5
- 241001465754 Metazoa Species 0.000 description 5
- 102100021286 Multiple PDZ domain protein Human genes 0.000 description 5
- 101710093002 Multiple PDZ domain protein Proteins 0.000 description 5
- 102100025254 Neurogenic locus notch homolog protein 4 Human genes 0.000 description 5
- 102100037001 Next to BRCA1 gene 1 protein Human genes 0.000 description 5
- 102000005650 Notch Receptors Human genes 0.000 description 5
- 108010070047 Notch Receptors Proteins 0.000 description 5
- 108090000163 Nuclear pore complex proteins Proteins 0.000 description 5
- 102000003789 Nuclear pore complex proteins Human genes 0.000 description 5
- 108700020796 Oncogene Proteins 0.000 description 5
- 102100026354 Paired mesoderm homeobox protein 2B Human genes 0.000 description 5
- 101710187408 Paired mesoderm homeobox protein 2B Proteins 0.000 description 5
- 102100039176 Pecanex-like protein 1 Human genes 0.000 description 5
- 102100023715 Poly(A)-specific ribonuclease PARN Human genes 0.000 description 5
- 102100033401 Probable ATP-dependent RNA helicase DDX31 Human genes 0.000 description 5
- 102100037169 Probable JmjC domain-containing histone demethylation protein 2C Human genes 0.000 description 5
- 102100034807 Programmed cell death protein 5 Human genes 0.000 description 5
- 108090000708 Proteasome Endopeptidase Complex Proteins 0.000 description 5
- 102000004245 Proteasome Endopeptidase Complex Human genes 0.000 description 5
- 102100024949 Protein CBFA2T2 Human genes 0.000 description 5
- 101710095100 Protocadherin Fat 2 Proteins 0.000 description 5
- 102100031426 Ras GTPase-activating protein 1 Human genes 0.000 description 5
- 102000004389 Ribonucleoproteins Human genes 0.000 description 5
- 108010081734 Ribonucleoproteins Proteins 0.000 description 5
- MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 description 5
- 102100021915 Sperm-associated antigen 5 Human genes 0.000 description 5
- 102100021393 Transcriptional repressor CTCFL Human genes 0.000 description 5
- 102100029611 Transient receptor potential cation channel subfamily V member 4 Human genes 0.000 description 5
- 108700039205 Transient receptor potential cation channel subfamily V member 4 Proteins 0.000 description 5
- 101710185494 Zinc finger protein Proteins 0.000 description 5
- 102100023597 Zinc finger protein 816 Human genes 0.000 description 5
- 230000004913 activation Effects 0.000 description 5
- 230000001464 adherent effect Effects 0.000 description 5
- 230000030741 antigen processing and presentation Effects 0.000 description 5
- 108091008324 binding proteins Proteins 0.000 description 5
- 239000000969 carrier Substances 0.000 description 5
- -1 clones Substances 0.000 description 5
- 239000002299 complementary DNA Substances 0.000 description 5
- 238000005516 engineering process Methods 0.000 description 5
- 238000004128 high performance liquid chromatography Methods 0.000 description 5
- 208000032839 leukemia Diseases 0.000 description 5
- 210000004072 lung Anatomy 0.000 description 5
- 239000011159 matrix material Substances 0.000 description 5
- 239000002609 medium Substances 0.000 description 5
- 230000007935 neutral effect Effects 0.000 description 5
- 150000007523 nucleic acids Chemical class 0.000 description 5
- 108010014186 ras Proteins Proteins 0.000 description 5
- 102000016914 ras Proteins Human genes 0.000 description 5
- 238000004007 reversed phase HPLC Methods 0.000 description 5
- 239000011780 sodium chloride Substances 0.000 description 5
- 239000000126 substance Substances 0.000 description 5
- 230000014621 translational initiation Effects 0.000 description 5
- 239000000439 tumor marker Substances 0.000 description 5
- 102100031251 1-acylglycerol-3-phosphate O-acyltransferase PNPLA3 Human genes 0.000 description 4
- 102100033714 40S ribosomal protein S6 Human genes 0.000 description 4
- 101710107638 40S ribosomal protein S6 Proteins 0.000 description 4
- 102100034482 AP-1 complex subunit beta-1 Human genes 0.000 description 4
- 101710166029 AP-1 complex subunit beta-1 Proteins 0.000 description 4
- 108050005774 APOBEC1 complementation factor Proteins 0.000 description 4
- 102100033618 ATP-binding cassette sub-family A member 2 Human genes 0.000 description 4
- 108700036213 ATP-binding cassette subfamily A member 2 Proteins 0.000 description 4
- 102100023388 ATP-dependent RNA helicase DHX15 Human genes 0.000 description 4
- 102100036441 Amyloid-beta A4 precursor protein-binding family A member 2 Human genes 0.000 description 4
- 101710093616 Amyloid-beta A4 precursor protein-binding family A member 2 Proteins 0.000 description 4
- 102100036818 Ankyrin-2 Human genes 0.000 description 4
- 101710191052 Ankyrin-2 Proteins 0.000 description 4
- 102100030765 Apolipoprotein L4 Human genes 0.000 description 4
- 102100033653 Arf-GAP with Rho-GAP domain, ANK repeat and PH domain-containing protein 2 Human genes 0.000 description 4
- 101710144522 Arf-GAP with Rho-GAP domain, ANK repeat and PH domain-containing protein 2 Proteins 0.000 description 4
- 102000030907 Aspartate Carbamoyltransferase Human genes 0.000 description 4
- 102000036365 BRCA1 Human genes 0.000 description 4
- 108700020463 BRCA1 Proteins 0.000 description 4
- 102100027882 Bardet-Biedl syndrome 7 protein Human genes 0.000 description 4
- 108010038940 CD48 Antigen Proteins 0.000 description 4
- 102100035671 Cadherin EGF LAG seven-pass G-type receptor 3 Human genes 0.000 description 4
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 4
- 108010052495 Calgranulin B Proteins 0.000 description 4
- 102100024966 Caspase recruitment domain-containing protein 10 Human genes 0.000 description 4
- 101710121715 Centrosomal protein of 70 kDa Proteins 0.000 description 4
- 102100039219 Centrosome-associated protein CEP250 Human genes 0.000 description 4
- 101710110151 Centrosome-associated protein CEP250 Proteins 0.000 description 4
- 108091006146 Channels Proteins 0.000 description 4
- 102100026099 Claudin domain-containing protein 1 Human genes 0.000 description 4
- 102100026735 Coagulation factor VIII Human genes 0.000 description 4
- 102100032373 Coiled-coil domain-containing protein 85B Human genes 0.000 description 4
- 102100025522 Cullin-7 Human genes 0.000 description 4
- 101710094593 Cullin-7 Proteins 0.000 description 4
- 101710110138 Cysteine protease ATG4B Proteins 0.000 description 4
- 102100021903 Cysteine protease ATG4B Human genes 0.000 description 4
- 102000053602 DNA Human genes 0.000 description 4
- 102100036674 DNA damage-binding protein 1 Human genes 0.000 description 4
- 101710156077 DNA damage-inducible transcript 3 protein Proteins 0.000 description 4
- 102100036262 DNA polymerase alpha subunit B Human genes 0.000 description 4
- 101710119478 DNA polymerase alpha subunit B Proteins 0.000 description 4
- 102100039116 DNA repair protein RAD50 Human genes 0.000 description 4
- 102100030960 DNA replication licensing factor MCM2 Human genes 0.000 description 4
- 102100024361 Disintegrin and metalloproteinase domain-containing protein 9 Human genes 0.000 description 4
- 101710116121 Disintegrin and metalloproteinase domain-containing protein 9 Proteins 0.000 description 4
- 102100038509 E3 ubiquitin-protein ligase ARIH1 Human genes 0.000 description 4
- 101710165507 E3 ubiquitin-protein ligase ARIH1 Proteins 0.000 description 4
- 102000001301 EGF receptor Human genes 0.000 description 4
- 108060006698 EGF receptor Proteins 0.000 description 4
- 102100032065 EMILIN-3 Human genes 0.000 description 4
- 102100021598 Endoplasmic reticulum aminopeptidase 1 Human genes 0.000 description 4
- 101710168245 Endoplasmic reticulum aminopeptidase 1 Proteins 0.000 description 4
- 101710143764 Epithelial membrane protein 3 Proteins 0.000 description 4
- 108010054218 Factor VIII Proteins 0.000 description 4
- 102100023513 Flotillin-2 Human genes 0.000 description 4
- 101710164820 Flotillin-2 Proteins 0.000 description 4
- 101710086299 Fructose-2,6-bisphosphatase Proteins 0.000 description 4
- 102100027269 Fructose-bisphosphate aldolase C Human genes 0.000 description 4
- 102100034265 GEM-interacting protein Human genes 0.000 description 4
- 101710102635 GEM-interacting protein Proteins 0.000 description 4
- 101710176449 GRIP and coiled-coil domain-containing protein 2 Proteins 0.000 description 4
- 102100041033 Golgin subfamily B member 1 Human genes 0.000 description 4
- 102100039619 Granulocyte colony-stimulating factor Human genes 0.000 description 4
- 102100026973 Heat shock protein 75 kDa, mitochondrial Human genes 0.000 description 4
- 102000000324 Heat shock protein beta-3 Human genes 0.000 description 4
- 108050008774 Heat shock protein beta-3 Proteins 0.000 description 4
- 108010004889 Heat-Shock Proteins Proteins 0.000 description 4
- 102000002812 Heat-Shock Proteins Human genes 0.000 description 4
- 108010018924 Heme Oxygenase-1 Proteins 0.000 description 4
- 101710184069 Hepatocyte growth factor receptor Proteins 0.000 description 4
- 102100024228 High affinity cAMP-specific and IBMX-insensitive 3',5'-cyclic phosphodiesterase 8A Human genes 0.000 description 4
- 101000894690 Homo sapiens BCL-6 corepressor Proteins 0.000 description 4
- 101000761182 Homo sapiens Caspase recruitment domain-containing protein 10 Proteins 0.000 description 4
- 101001058870 Homo sapiens GRIP and coiled-coil domain-containing protein 2 Proteins 0.000 description 4
- 101001117261 Homo sapiens High affinity cAMP-specific and IBMX-insensitive 3',5'-cyclic phosphodiesterase 8A Proteins 0.000 description 4
- 101001037191 Homo sapiens Hyaluronan synthase 1 Proteins 0.000 description 4
- 101000599573 Homo sapiens InaD-like protein Proteins 0.000 description 4
- 101001063456 Homo sapiens Leucine-rich repeat-containing G-protein coupled receptor 5 Proteins 0.000 description 4
- 101001019117 Homo sapiens Mediator of RNA polymerase II transcription subunit 23 Proteins 0.000 description 4
- 101001057133 Homo sapiens Melanoma-associated antigen E2 Proteins 0.000 description 4
- 101000583811 Homo sapiens Mitotic spindle assembly checkpoint protein MAD2B Proteins 0.000 description 4
- 101000978766 Homo sapiens Neurogenic locus notch homolog protein 1 Proteins 0.000 description 4
- 101000578287 Homo sapiens Non-POU domain-containing octamer-binding protein Proteins 0.000 description 4
- 101001118493 Homo sapiens Nuclear pore glycoprotein p62 Proteins 0.000 description 4
- 101000870734 Homo sapiens Probable ATP-dependent RNA helicase DDX31 Proteins 0.000 description 4
- 101001028703 Homo sapiens Probable JmjC domain-containing histone demethylation protein 2C Proteins 0.000 description 4
- 101000657350 Homo sapiens RNA-splicing ligase RtcB homolog Proteins 0.000 description 4
- 101001106045 Homo sapiens Regulator of nonsense transcripts 2 Proteins 0.000 description 4
- 101000904787 Homo sapiens Serine/threonine-protein kinase ATR Proteins 0.000 description 4
- 101000661457 Homo sapiens Serine/threonine/tyrosine-interacting-like protein 1 Proteins 0.000 description 4
- 101000932572 Homo sapiens Uncharacterized protein C3orf62 Proteins 0.000 description 4
- 101000784544 Homo sapiens Zinc finger and SCAN domain-containing protein 20 Proteins 0.000 description 4
- 102100040203 Hyaluronan synthase 1 Human genes 0.000 description 4
- 101710086664 Importin-13 Proteins 0.000 description 4
- 102100036404 Inositol-trisphosphate 3-kinase B Human genes 0.000 description 4
- 102000000510 Integrin alpha3 Human genes 0.000 description 4
- 102000012334 Integrin beta4 Human genes 0.000 description 4
- 108010050904 Interferons Proteins 0.000 description 4
- 102000014150 Interferons Human genes 0.000 description 4
- 108010066327 Keratin-18 Proteins 0.000 description 4
- AYFVYJQAPQTCCC-GBXIJSLDSA-N L-threonine Chemical compound C[C@@H](O)[C@H](N)C(O)=O AYFVYJQAPQTCCC-GBXIJSLDSA-N 0.000 description 4
- OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 description 4
- 102100038235 Large neutral amino acids transporter small subunit 2 Human genes 0.000 description 4
- 102100030657 Lethal(3)malignant brain tumor-like protein 1 Human genes 0.000 description 4
- 101710173086 Lethal(3)malignant brain tumor-like protein 1 Proteins 0.000 description 4
- 108010006444 Leucine-Rich Repeat Proteins Proteins 0.000 description 4
- 102100032655 Leucine-rich repeat neuronal protein 1 Human genes 0.000 description 4
- 101710164331 Leucine-rich repeat neuronal protein 1 Proteins 0.000 description 4
- 102100033246 Lysine-specific demethylase 5A Human genes 0.000 description 4
- 102100022819 MHC class II regulatory factor RFX1 Human genes 0.000 description 4
- 102100037791 Macrophage migration inhibitory factor Human genes 0.000 description 4
- 102100040888 Malignant T-cell-amplified sequence 1 Human genes 0.000 description 4
- 102100025077 Melanoma-associated antigen 4 Human genes 0.000 description 4
- 102100026158 Melanophilin Human genes 0.000 description 4
- 101710158003 Melanophilin Proteins 0.000 description 4
- 102000005741 Metalloproteases Human genes 0.000 description 4
- 108010006035 Metalloproteases Proteins 0.000 description 4
- 102000009664 Microtubule-Associated Proteins Human genes 0.000 description 4
- 108010020004 Microtubule-Associated Proteins Proteins 0.000 description 4
- 108010079782 Minichromosome Maintenance Complex Component 2 Proteins 0.000 description 4
- 102100030955 Mitotic spindle assembly checkpoint protein MAD2B Human genes 0.000 description 4
- 241000699666 Mus <mouse, genus> Species 0.000 description 4
- 102100034099 Myocardin-related transcription factor A Human genes 0.000 description 4
- 101710132126 Myocardin-related transcription factor A Proteins 0.000 description 4
- 102100032971 Myomesin-1 Human genes 0.000 description 4
- 102000005604 Myosin Heavy Chains Human genes 0.000 description 4
- 108010084498 Myosin Heavy Chains Proteins 0.000 description 4
- 102100023121 Ninein Human genes 0.000 description 4
- 101710196576 Ninein Proteins 0.000 description 4
- 102100028102 Non-POU domain-containing octamer-binding protein Human genes 0.000 description 4
- 102100024057 Nuclear pore glycoprotein p62 Human genes 0.000 description 4
- 102100021079 Ornithine decarboxylase Human genes 0.000 description 4
- 108010044843 Peptide Initiation Factors Proteins 0.000 description 4
- 102000005877 Peptide Initiation Factors Human genes 0.000 description 4
- 102100026131 Peptidyl-prolyl cis-trans isomerase A-like 4D Human genes 0.000 description 4
- 108090000430 Phosphatidylinositol 3-kinases Proteins 0.000 description 4
- 102000003993 Phosphatidylinositol 3-kinases Human genes 0.000 description 4
- 102100034382 Plexin-A1 Human genes 0.000 description 4
- 102100034383 Plexin-B2 Human genes 0.000 description 4
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 4
- 102100028729 Pre-mRNA-splicing factor ATP-dependent RNA helicase PRP16 Human genes 0.000 description 4
- 108030004374 Proline-tRNA ligases Proteins 0.000 description 4
- 102100040477 Prolyl 4-hydroxylase subunit alpha-1 Human genes 0.000 description 4
- 102100026034 Protein BTG2 Human genes 0.000 description 4
- 101710175506 Protein CBFA2T2 Proteins 0.000 description 4
- 102100033954 Protein PRRC2A Human genes 0.000 description 4
- 108010089836 Proto-Oncogene Proteins c-met Proteins 0.000 description 4
- 102100034776 RNA-splicing ligase RtcB homolog Human genes 0.000 description 4
- 108050004017 Ras GTPase-activating protein 1 Proteins 0.000 description 4
- 102100040854 Ras GTPase-activating protein-binding protein 1 Human genes 0.000 description 4
- 108050003637 Ras GTPase-activating protein-binding protein 1 Proteins 0.000 description 4
- 102100038042 Retinoblastoma-associated protein Human genes 0.000 description 4
- 101710124357 Retinoblastoma-associated protein Proteins 0.000 description 4
- 102100021446 Rho GTPase-activating protein 7 Human genes 0.000 description 4
- 102100027055 Ribosome biogenesis protein BOP1 Human genes 0.000 description 4
- 101710186223 Ribosome biogenesis protein BOP1 Proteins 0.000 description 4
- 108050007572 S-phase kinase-associated protein 1 Proteins 0.000 description 4
- 102100037782 Serine/threonine/tyrosine-interacting-like protein 1 Human genes 0.000 description 4
- 102100030733 Set1/Ash2 histone methyltransferase complex subunit ASH2 Human genes 0.000 description 4
- 102100035002 Synaptotagmin-like protein 4 Human genes 0.000 description 4
- 101710156031 Synaptotagmin-like protein 4 Proteins 0.000 description 4
- 101710103331 Telomere-associated protein RIF1 Proteins 0.000 description 4
- 102100037806 Telomere-associated protein RIF1 Human genes 0.000 description 4
- 102100036987 Transmembrane protein 115 Human genes 0.000 description 4
- 239000007983 Tris buffer Substances 0.000 description 4
- 102100033579 Trophoblast glycoprotein Human genes 0.000 description 4
- 101710190034 Trophoblast glycoprotein Proteins 0.000 description 4
- 108060008682 Tumor Necrosis Factor Proteins 0.000 description 4
- 102000000852 Tumor Necrosis Factor-alpha Human genes 0.000 description 4
- 102100031988 Tumor necrosis factor ligand superfamily member 6 Human genes 0.000 description 4
- 102100024248 Tumor suppressor candidate 3 Human genes 0.000 description 4
- 102100027958 UDP-GalNAc:beta-1,3-N-acetylgalactosaminyltransferase 2 Human genes 0.000 description 4
- 102100037921 UDP-N-acetylglucosamine pyrophosphorylase Human genes 0.000 description 4
- LFTYTUAZOPRMMI-UHFFFAOYSA-N UNPD164450 Natural products O1C(CO)C(O)C(O)C(NC(=O)C)C1OP(O)(=O)OP(O)(=O)OCC1C(O)C(O)C(N2C(NC(=O)C=C2)=O)O1 LFTYTUAZOPRMMI-UHFFFAOYSA-N 0.000 description 4
- 102100030434 Ubiquitin-protein ligase E3A Human genes 0.000 description 4
- 102100025713 Uncharacterized protein C3orf62 Human genes 0.000 description 4
- 102000009519 Vascular Endothelial Growth Factor D Human genes 0.000 description 4
- 108010073919 Vascular Endothelial Growth Factor D Proteins 0.000 description 4
- 102100033178 Vascular endothelial growth factor receptor 1 Human genes 0.000 description 4
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 4
- 101710082115 Zinc finger and SCAN domain-containing protein 20 Proteins 0.000 description 4
- 102100023895 Zyxin Human genes 0.000 description 4
- 239000002253 acid Substances 0.000 description 4
- 239000004480 active ingredient Substances 0.000 description 4
- 238000004458 analytical method Methods 0.000 description 4
- 239000011575 calcium Substances 0.000 description 4
- 229910052791 calcium Inorganic materials 0.000 description 4
- 108010014510 connexin 40 Proteins 0.000 description 4
- 238000012258 culturing Methods 0.000 description 4
- 230000001086 cytosolic effect Effects 0.000 description 4
- 239000012636 effector Substances 0.000 description 4
- 150000002148 esters Chemical class 0.000 description 4
- 239000012091 fetal bovine serum Substances 0.000 description 4
- 108010025934 hnRNP A2 Proteins 0.000 description 4
- 230000036039 immunity Effects 0.000 description 4
- 230000003053 immunization Effects 0.000 description 4
- 238000002649 immunization Methods 0.000 description 4
- 239000003112 inhibitor Substances 0.000 description 4
- 229940079322 interferon Drugs 0.000 description 4
- 102000004114 interleukin 20 Human genes 0.000 description 4
- 238000004519 manufacturing process Methods 0.000 description 4
- 239000003550 marker Substances 0.000 description 4
- 230000000394 mitotic effect Effects 0.000 description 4
- 239000002773 nucleotide Substances 0.000 description 4
- 125000003729 nucleotide group Chemical group 0.000 description 4
- 230000002611 ovarian Effects 0.000 description 4
- 210000005259 peripheral blood Anatomy 0.000 description 4
- 239000011886 peripheral blood Substances 0.000 description 4
- 239000013612 plasmid Substances 0.000 description 4
- 230000008488 polyadenylation Effects 0.000 description 4
- 238000002360 preparation method Methods 0.000 description 4
- 238000000746 purification Methods 0.000 description 4
- 125000006850 spacer group Chemical group 0.000 description 4
- 239000000758 substrate Substances 0.000 description 4
- 101710098726 tRNA wybutosine-synthesizing protein 4 Proteins 0.000 description 4
- 102100020799 tRNA wybutosine-synthesizing protein 4 Human genes 0.000 description 4
- 210000001519 tissue Anatomy 0.000 description 4
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 4
- 229910052725 zinc Inorganic materials 0.000 description 4
- 239000011701 zinc Substances 0.000 description 4
- 102100023439 ATP-dependent RNA helicase DHX29 Human genes 0.000 description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- 102100022523 Acetoacetyl-CoA synthetase Human genes 0.000 description 3
- 102100026441 Adhesion G-protein coupled receptor D1 Human genes 0.000 description 3
- 102100040036 Adhesion G-protein coupled receptor G4 Human genes 0.000 description 3
- 101710096376 Adhesion G-protein coupled receptor G4 Proteins 0.000 description 3
- 102100032956 Alpha-actinin-3 Human genes 0.000 description 3
- 101710115089 Alpha-actinin-3 Proteins 0.000 description 3
- 102000003730 Alpha-catenin Human genes 0.000 description 3
- 108090000020 Alpha-catenin Proteins 0.000 description 3
- 108090000915 Aminopeptidases Proteins 0.000 description 3
- 102000004400 Aminopeptidases Human genes 0.000 description 3
- 101000917306 Arabidopsis thaliana Fatty acyl-CoA reductase 2, chloroplastic Proteins 0.000 description 3
- 108700000712 BH3 Interacting Domain Death Agonist Proteins 0.000 description 3
- 102100035740 BH3-interacting domain death agonist Human genes 0.000 description 3
- 102100025371 Butyrophilin-like protein 8 Human genes 0.000 description 3
- 101710140589 Butyrophilin-like protein 8 Proteins 0.000 description 3
- 102000005643 COP9 Signalosome Complex Human genes 0.000 description 3
- 108010070033 COP9 Signalosome Complex Proteins 0.000 description 3
- 102100031272 Calcineurin B homologous protein 2 Human genes 0.000 description 3
- 102100028003 Catenin alpha-1 Human genes 0.000 description 3
- 102100031441 Cell cycle checkpoint protein RAD17 Human genes 0.000 description 3
- 102100023508 Chloride intracellular channel protein 4 Human genes 0.000 description 3
- 101710185644 Chloride intracellular channel protein 4 Proteins 0.000 description 3
- 108010077544 Chromatin Proteins 0.000 description 3
- 102100024889 Cytochrome P450 2E1 Human genes 0.000 description 3
- 102000016928 DNA-directed DNA polymerase Human genes 0.000 description 3
- 108010014303 DNA-directed DNA polymerase Proteins 0.000 description 3
- 101800001224 Disintegrin Proteins 0.000 description 3
- 102100024101 DnaJ homolog subfamily C member 28 Human genes 0.000 description 3
- 108010012830 Dynactin Complex Proteins 0.000 description 3
- 102000019205 Dynactin Complex Human genes 0.000 description 3
- 102100034745 E3 ubiquitin-protein ligase HERC2 Human genes 0.000 description 3
- 101710197780 E3 ubiquitin-protein ligase LAP Proteins 0.000 description 3
- 102100039246 Elongator complex protein 1 Human genes 0.000 description 3
- 101710167754 Elongator complex protein 1 Proteins 0.000 description 3
- 102100039328 Endoplasmin Human genes 0.000 description 3
- 101710128765 Enhancer of filamentation 1 Proteins 0.000 description 3
- 102100028166 FACT complex subunit SSRP1 Human genes 0.000 description 3
- 101710100450 FACT complex subunit SSRP1 Proteins 0.000 description 3
- 102100038636 FYVE, RhoGEF and PH domain-containing protein 2 Human genes 0.000 description 3
- 102000001690 Factor VIII Human genes 0.000 description 3
- 102100029595 Fatty acyl-CoA reductase 2 Human genes 0.000 description 3
- 102000018233 Fibroblast Growth Factor Human genes 0.000 description 3
- 108050007372 Fibroblast Growth Factor Proteins 0.000 description 3
- 102100027844 Fibroblast growth factor receptor 4 Human genes 0.000 description 3
- 101710182387 Fibroblast growth factor receptor 4 Proteins 0.000 description 3
- 102100026561 Filamin-A Human genes 0.000 description 3
- 101710091743 Filamin-A Proteins 0.000 description 3
- 101710199249 GTP-binding protein Rhes Proteins 0.000 description 3
- 102100033369 Glutathione S-transferase A4 Human genes 0.000 description 3
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 3
- 102100023911 Growth factor receptor-bound protein 14 Human genes 0.000 description 3
- 108050000445 Growth factor receptor-bound protein 14 Proteins 0.000 description 3
- 102100039256 Growth hormone secretagogue receptor type 1 Human genes 0.000 description 3
- 108010086377 HLA-A3 Antigen Proteins 0.000 description 3
- 101710130649 Heat shock protein 75 kDa, mitochondrial Proteins 0.000 description 3
- 101800000791 Hemagglutinin-esterase-fusion glycoprotein chain 1 Proteins 0.000 description 3
- 102100027743 Heterogeneous nuclear ribonucleoprotein C-like 1 Human genes 0.000 description 3
- 102100038030 High affinity immunoglobulin alpha and immunoglobulin mu Fc receptor Human genes 0.000 description 3
- 101710136666 High affinity immunoglobulin alpha and immunoglobulin mu Fc receptor Proteins 0.000 description 3
- 101710098641 Histatin-1 Proteins 0.000 description 3
- 102100038720 Histone deacetylase 9 Human genes 0.000 description 3
- 101710177326 Histone deacetylase 9 Proteins 0.000 description 3
- 102100022102 Histone-lysine N-methyltransferase 2B Human genes 0.000 description 3
- 101710118576 Histone-lysine N-methyltransferase 2B Proteins 0.000 description 3
- 101710163642 Homeobox protein PKNOX1 Proteins 0.000 description 3
- 102100029394 Homeobox protein PKNOX1 Human genes 0.000 description 3
- 101000694288 Homo sapiens 40S ribosomal protein SA Proteins 0.000 description 3
- 101000907886 Homo sapiens ATP-dependent RNA helicase DHX15 Proteins 0.000 description 3
- 101000907919 Homo sapiens ATP-dependent RNA helicase DHX29 Proteins 0.000 description 3
- 101001053999 Homo sapiens DnaJ homolog subfamily C member 28 Proteins 0.000 description 3
- 101000872516 Homo sapiens E3 ubiquitin-protein ligase HERC2 Proteins 0.000 description 3
- 101000812663 Homo sapiens Endoplasmin Proteins 0.000 description 3
- 101001011788 Homo sapiens Epithelial membrane protein 3 Proteins 0.000 description 3
- 101001031749 Homo sapiens FYVE, RhoGEF and PH domain-containing protein 2 Proteins 0.000 description 3
- 101000917301 Homo sapiens Fatty acyl-CoA reductase 2 Proteins 0.000 description 3
- 101000578396 Homo sapiens GTP-binding protein Rhes Proteins 0.000 description 3
- 101000870514 Homo sapiens Glutathione S-transferase A4 Proteins 0.000 description 3
- 101001016856 Homo sapiens Heat shock protein HSP 90-beta Proteins 0.000 description 3
- 101001056699 Homo sapiens Intersectin-2 Proteins 0.000 description 3
- 101500026028 Homo sapiens Lamin-A/C Proteins 0.000 description 3
- 101000942713 Homo sapiens Liprin-alpha-2 Proteins 0.000 description 3
- 101001005720 Homo sapiens Melanoma-associated antigen 4 Proteins 0.000 description 3
- 101001120082 Homo sapiens P2Y purinoceptor 13 Proteins 0.000 description 3
- 101000609943 Homo sapiens Pecanex-like protein 1 Proteins 0.000 description 3
- 101001122811 Homo sapiens Pre-mRNA-splicing factor ATP-dependent RNA helicase PRP16 Proteins 0.000 description 3
- 101000734643 Homo sapiens Programmed cell death protein 5 Proteins 0.000 description 3
- 101000583797 Homo sapiens Protein MCM10 homolog Proteins 0.000 description 3
- 101000853457 Homo sapiens Ral GTPase-activating protein subunit beta Proteins 0.000 description 3
- 101000864057 Homo sapiens Serine/threonine-protein kinase SMG1 Proteins 0.000 description 3
- 101000914484 Homo sapiens T-lymphocyte activation antigen CD80 Proteins 0.000 description 3
- 101000662009 Homo sapiens UDP-N-acetylglucosamine pyrophosphorylase Proteins 0.000 description 3
- 101000805481 Homo sapiens Vigilin Proteins 0.000 description 3
- 101000788891 Homo sapiens Zinc finger protein 280B Proteins 0.000 description 3
- 108010071021 Inositol-polyphosphate multikinase Proteins 0.000 description 3
- 108010072255 Integrin alpha3beta1 Proteins 0.000 description 3
- 108010074328 Interferon-gamma Proteins 0.000 description 3
- 102000013462 Interleukin-12 Human genes 0.000 description 3
- 108010065805 Interleukin-12 Proteins 0.000 description 3
- 108010002586 Interleukin-7 Proteins 0.000 description 3
- 102000000704 Interleukin-7 Human genes 0.000 description 3
- 101710088362 Intersectin-2 Proteins 0.000 description 3
- 102100022905 Keratin, type II cytoskeletal 1 Human genes 0.000 description 3
- 101710194922 Keratin, type II cytoskeletal 1 Proteins 0.000 description 3
- 108010081657 Ki antigen Proteins 0.000 description 3
- 102000019293 Kinesin-like proteins Human genes 0.000 description 3
- 108050006659 Kinesin-like proteins Proteins 0.000 description 3
- ZDXPYRJPNDTMRX-VKHMYHEASA-N L-glutamine Chemical compound OC(=O)[C@@H](N)CCC(N)=O ZDXPYRJPNDTMRX-VKHMYHEASA-N 0.000 description 3
- 101800000516 Lamin-A/C Proteins 0.000 description 3
- 102100034710 Laminin subunit gamma-1 Human genes 0.000 description 3
- 101710095658 Laminin subunit gamma-1 Proteins 0.000 description 3
- 101000988090 Leishmania donovani Heat shock protein 83 Proteins 0.000 description 3
- 108050001481 Liprin-alpha-2 Proteins 0.000 description 3
- 102100022494 Mucin-5B Human genes 0.000 description 3
- 108010030201 Mucin-5B Proteins 0.000 description 3
- 102000015728 Mucins Human genes 0.000 description 3
- 108010063954 Mucins Proteins 0.000 description 3
- 101000644563 Mus musculus tRNA wybutosine-synthesizing protein 4 Proteins 0.000 description 3
- 101710106571 Myomesin-1 Proteins 0.000 description 3
- 102100033013 Myosin-13 Human genes 0.000 description 3
- 101710115161 Myosin-13 Proteins 0.000 description 3
- 102100021153 Netrin receptor DCC Human genes 0.000 description 3
- 108700037638 Neurogenic locus notch homolog protein 1 Proteins 0.000 description 3
- 102100025247 Neurogenic locus notch homolog protein 3 Human genes 0.000 description 3
- 101710161854 Next to BRCA1 gene 1 protein Proteins 0.000 description 3
- 102100029438 Nitric oxide synthase, inducible Human genes 0.000 description 3
- 108010029756 Notch3 Receptor Proteins 0.000 description 3
- 102100021976 Nuclear pore complex protein Nup107 Human genes 0.000 description 3
- 101710191656 Nuclear pore complex protein Nup107 Proteins 0.000 description 3
- 102100025372 Nuclear pore complex protein Nup98-Nup96 Human genes 0.000 description 3
- 101800002013 Nucleoporin nup98 Proteins 0.000 description 3
- 108091034117 Oligonucleotide Proteins 0.000 description 3
- 108700005126 Ornithine decarboxylases Proteins 0.000 description 3
- 102100032151 Oxysterol-binding protein-related protein 8 Human genes 0.000 description 3
- 101710201622 Oxysterol-binding protein-related protein 8 Proteins 0.000 description 3
- 102100034925 P-selectin glycoprotein ligand 1 Human genes 0.000 description 3
- 102000012850 Patched-1 Receptor Human genes 0.000 description 3
- 108010065129 Patched-1 Receptor Proteins 0.000 description 3
- 108010022678 Phosphofructokinase-2 Proteins 0.000 description 3
- 101710133246 Poly(A)-specific ribonuclease PARN Proteins 0.000 description 3
- 101710146337 Pre-mRNA-splicing factor ATP-dependent RNA helicase PRP16 Proteins 0.000 description 3
- 102000004079 Prolyl Hydroxylases Human genes 0.000 description 3
- 108010043005 Prolyl Hydroxylases Proteins 0.000 description 3
- 102000001253 Protein Kinase Human genes 0.000 description 3
- 102100030962 Protein MCM10 homolog Human genes 0.000 description 3
- 101710098724 Protein alpha-2 Proteins 0.000 description 3
- 101710150593 Protein beta Proteins 0.000 description 3
- 101710161390 Protein patched homolog 1 Proteins 0.000 description 3
- 102100028680 Protein patched homolog 1 Human genes 0.000 description 3
- 102100029258 Protocadherin gamma-A10 Human genes 0.000 description 3
- 101710142869 Protocadherin gamma-A10 Proteins 0.000 description 3
- 101710142883 Protocadherin gamma-A12 Proteins 0.000 description 3
- 102100020784 RCC1-like G exchanging factor-like protein Human genes 0.000 description 3
- 101710091740 RCC1-like G exchanging factor-like protein Proteins 0.000 description 3
- 230000004570 RNA-binding Effects 0.000 description 3
- 102100035887 Ral GTPase-activating protein subunit beta Human genes 0.000 description 3
- 102100036261 Regulating synaptic membrane exocytosis protein 3 Human genes 0.000 description 3
- 101710108506 Regulating synaptic membrane exocytosis protein 3 Proteins 0.000 description 3
- 108010053823 Rho Guanine Nucleotide Exchange Factors Proteins 0.000 description 3
- 102100035066 Ribosomal L1 domain-containing protein 1 Human genes 0.000 description 3
- 102000019027 Ryanodine Receptor Calcium Release Channel Human genes 0.000 description 3
- 206010039491 Sarcoma Diseases 0.000 description 3
- 102000014105 Semaphorin Human genes 0.000 description 3
- 108050003978 Semaphorin Proteins 0.000 description 3
- 101710098571 Sperm-associated antigen 5 Proteins 0.000 description 3
- 108010085012 Steroid Receptors Proteins 0.000 description 3
- 102100028679 T-complex protein 1 subunit beta Human genes 0.000 description 3
- 101710085986 T-complex protein 1 subunit beta Proteins 0.000 description 3
- 102100029886 T-complex protein 1 subunit epsilon Human genes 0.000 description 3
- 101710186197 T-complex protein 1 subunit epsilon Proteins 0.000 description 3
- 102100027222 T-lymphocyte activation antigen CD80 Human genes 0.000 description 3
- 102100040296 TATA-box-binding protein Human genes 0.000 description 3
- 102100035240 Taste receptor type 2 member 40 Human genes 0.000 description 3
- 102100034475 Tastin Human genes 0.000 description 3
- 101710197164 Tastin Proteins 0.000 description 3
- 102100031022 Telomerase-binding protein EST1A Human genes 0.000 description 3
- AYFVYJQAPQTCCC-UHFFFAOYSA-N Threonine Natural products CC(O)C(N)C(O)=O AYFVYJQAPQTCCC-UHFFFAOYSA-N 0.000 description 3
- 239000004473 Threonine Substances 0.000 description 3
- 108010083268 Transcription Factor TFIID Proteins 0.000 description 3
- 101710128101 Transcriptional repressor CTCFL Proteins 0.000 description 3
- 102100034300 Tryptophan-tRNA ligase, cytoplasmic Human genes 0.000 description 3
- 101710106597 U1 small nuclear ribonucleoprotein A Proteins 0.000 description 3
- 102100031287 Ubiquitin carboxyl-terminal hydrolase 3 Human genes 0.000 description 3
- 101710167632 Ubiquitin carboxyl-terminal hydrolase 3 Proteins 0.000 description 3
- 102100038932 Unconventional myosin-XVIIIa Human genes 0.000 description 3
- 108010053096 Vascular Endothelial Growth Factor Receptor-1 Proteins 0.000 description 3
- 102100037814 Vigilin Human genes 0.000 description 3
- 102100025301 Zinc finger protein 280B Human genes 0.000 description 3
- 108010012842 acetoacetyl-CoA synthetase Proteins 0.000 description 3
- 125000001931 aliphatic group Chemical group 0.000 description 3
- 210000003567 ascitic fluid Anatomy 0.000 description 3
- 210000003719 b-lymphocyte Anatomy 0.000 description 3
- 230000001580 bacterial effect Effects 0.000 description 3
- 210000004556 brain Anatomy 0.000 description 3
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 3
- 230000003197 catalytic effect Effects 0.000 description 3
- 238000004113 cell culture Methods 0.000 description 3
- 210000003483 chromatin Anatomy 0.000 description 3
- 230000000295 complement effect Effects 0.000 description 3
- 210000000805 cytoplasm Anatomy 0.000 description 3
- 238000002784 cytotoxicity assay Methods 0.000 description 3
- 231100000263 cytotoxicity test Toxicity 0.000 description 3
- LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 3
- 239000003814 drug Substances 0.000 description 3
- 239000003937 drug carrier Substances 0.000 description 3
- 102000013035 dynein heavy chain Human genes 0.000 description 3
- 108060002430 dynein heavy chain Proteins 0.000 description 3
- 238000004520 electroporation Methods 0.000 description 3
- 229940126864 fibroblast growth factor Drugs 0.000 description 3
- 102000010660 flotillin Human genes 0.000 description 3
- 108060000864 flotillin Proteins 0.000 description 3
- 238000005194 fractionation Methods 0.000 description 3
- 230000004927 fusion Effects 0.000 description 3
- 102000009543 guanyl-nucleotide exchange factor activity proteins Human genes 0.000 description 3
- 206010073071 hepatocellular carcinoma Diseases 0.000 description 3
- 210000000987 immune system Anatomy 0.000 description 3
- 230000002401 inhibitory effect Effects 0.000 description 3
- 230000002147 killing effect Effects 0.000 description 3
- 108010090909 laminin gamma 1 Proteins 0.000 description 3
- 231100000518 lethal Toxicity 0.000 description 3
- 230000001665 lethal effect Effects 0.000 description 3
- 239000003446 ligand Substances 0.000 description 3
- 150000002632 lipids Chemical class 0.000 description 3
- SQEHCNOBYLQFTG-UHFFFAOYSA-M lithium;thiophene-2-carboxylate Chemical compound [Li+].[O-]C(=O)C1=CC=CS1 SQEHCNOBYLQFTG-UHFFFAOYSA-M 0.000 description 3
- 201000005202 lung cancer Diseases 0.000 description 3
- 208000020816 lung neoplasm Diseases 0.000 description 3
- 210000001165 lymph node Anatomy 0.000 description 3
- 210000002540 macrophage Anatomy 0.000 description 3
- 230000005012 migration Effects 0.000 description 3
- 238000013508 migration Methods 0.000 description 3
- 235000021243 milk fat Nutrition 0.000 description 3
- 238000010369 molecular cloning Methods 0.000 description 3
- 238000012544 monitoring process Methods 0.000 description 3
- 210000001616 monocyte Anatomy 0.000 description 3
- 210000004165 myocardium Anatomy 0.000 description 3
- 210000001577 neostriatum Anatomy 0.000 description 3
- 230000001272 neurogenic effect Effects 0.000 description 3
- 102000039446 nucleic acids Human genes 0.000 description 3
- 108020004707 nucleic acids Proteins 0.000 description 3
- 239000008188 pellet Substances 0.000 description 3
- 108010044156 peptidyl-prolyl cis-trans isomerase b Proteins 0.000 description 3
- 108010063864 phenylpyruvate tautomerase Proteins 0.000 description 3
- 239000002953 phosphate buffered saline Substances 0.000 description 3
- 238000012545 processing Methods 0.000 description 3
- 108060006633 protein kinase Proteins 0.000 description 3
- 238000012216 screening Methods 0.000 description 3
- 238000000926 separation method Methods 0.000 description 3
- 239000007787 solid Substances 0.000 description 3
- 241000894007 species Species 0.000 description 3
- 230000002269 spontaneous effect Effects 0.000 description 3
- 102000005969 steroid hormone receptors Human genes 0.000 description 3
- 239000006228 supernatant Substances 0.000 description 3
- 239000004094 surface-active agent Substances 0.000 description 3
- 230000008685 targeting Effects 0.000 description 3
- 108091008744 testicular receptors 2 Proteins 0.000 description 3
- 230000001225 therapeutic effect Effects 0.000 description 3
- 230000005026 transcription initiation Effects 0.000 description 3
- OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 3
- 239000013603 viral vector Substances 0.000 description 3
- 101150084750 1 gene Proteins 0.000 description 2
- 108010017836 1,3-alpha-D-glucan synthase Proteins 0.000 description 2
- 108050003337 1-acylglycerol-3-phosphate O-acyltransferase PNPLA3 Proteins 0.000 description 2
- 102100035389 2'-5'-oligoadenylate synthase 3 Human genes 0.000 description 2
- MSWZFWKMSRAUBD-IVMDWMLBSA-N 2-amino-2-deoxy-D-glucopyranose Chemical compound N[C@H]1C(O)O[C@H](CO)[C@@H](O)[C@@H]1O MSWZFWKMSRAUBD-IVMDWMLBSA-N 0.000 description 2
- 102100036734 26S proteasome non-ATPase regulatory subunit 10 Human genes 0.000 description 2
- 101710113902 26S proteasome non-ATPase regulatory subunit 10 Proteins 0.000 description 2
- 108010027312 26S proteasome non-ATPase regulatory subunit 13 Proteins 0.000 description 2
- 102100040962 26S proteasome non-ATPase regulatory subunit 13 Human genes 0.000 description 2
- 102100022644 26S proteasome regulatory subunit 4 Human genes 0.000 description 2
- 102100031571 40S ribosomal protein S16 Human genes 0.000 description 2
- 101710131774 40S ribosomal protein S16 Proteins 0.000 description 2
- 102100022600 40S ribosomal protein S3a Human genes 0.000 description 2
- 101710131943 40S ribosomal protein S3a Proteins 0.000 description 2
- 102100033731 40S ribosomal protein S9 Human genes 0.000 description 2
- 101710107647 40S ribosomal protein S9 Proteins 0.000 description 2
- 108050007366 40S ribosomal protein SA Proteins 0.000 description 2
- 102000017509 APOBEC1 complementation factor Human genes 0.000 description 2
- 102100033311 APOBEC1 complementation factor Human genes 0.000 description 2
- 102100030841 AT-rich interactive domain-containing protein 4A Human genes 0.000 description 2
- 102100027782 ATP synthase-coupling factor 6, mitochondrial Human genes 0.000 description 2
- 102100022654 ATP-binding cassette sub-family F member 2 Human genes 0.000 description 2
- 101710139796 ATP-dependent DNA helicase DDX11 Proteins 0.000 description 2
- 101710140082 ATP-dependent RNA helicase DHX15 Proteins 0.000 description 2
- 101710159080 Aconitate hydratase A Proteins 0.000 description 2
- 101710159078 Aconitate hydratase B Proteins 0.000 description 2
- 102100022900 Actin, cytoplasmic 1 Human genes 0.000 description 2
- 101710119043 Actin, cytoplasmic 1 Proteins 0.000 description 2
- 102100028100 Activating signal cointegrator 1 Human genes 0.000 description 2
- 101710089542 Activating signal cointegrator 1 Proteins 0.000 description 2
- 101710191686 Activin receptor type-2A Proteins 0.000 description 2
- 102100026661 Activity-dependent neuroprotector homeobox protein 2 Human genes 0.000 description 2
- 206010000830 Acute leukaemia Diseases 0.000 description 2
- 101710096319 Adhesion G-protein coupled receptor D1 Proteins 0.000 description 2
- 102100030461 Alpha-ketoglutarate-dependent dioxygenase FTO Human genes 0.000 description 2
- 102100022995 Ankyrin repeat domain-containing protein 18B Human genes 0.000 description 2
- 108050008801 Anoctamin-3 Proteins 0.000 description 2
- 102100023005 Anoctamin-3 Human genes 0.000 description 2
- 101710146736 Apolipoprotein L4 Proteins 0.000 description 2
- 101000640990 Arabidopsis thaliana Tryptophan-tRNA ligase, chloroplastic/mitochondrial Proteins 0.000 description 2
- 108010002493 Arachin Proteins 0.000 description 2
- 102000002785 Ataxin-10 Human genes 0.000 description 2
- 108010043914 Ataxin-10 Proteins 0.000 description 2
- 208000001992 Autosomal Dominant Optic Atrophy Diseases 0.000 description 2
- 102100035730 B-cell receptor-associated protein 31 Human genes 0.000 description 2
- 102100035656 BCL2/adenovirus E1B 19 kDa protein-interacting protein 3 Human genes 0.000 description 2
- 102100028048 BRCA1-associated RING domain protein 1 Human genes 0.000 description 2
- 108700020462 BRCA2 Proteins 0.000 description 2
- 102000052609 BRCA2 Human genes 0.000 description 2
- 102100035652 BRISC and BRCA1-A complex member 2 Human genes 0.000 description 2
- 101710086174 BRISC and BRCA1-A complex member 2 Proteins 0.000 description 2
- 101710181772 Bardet-Biedl syndrome 7 protein Proteins 0.000 description 2
- 102100033949 Basic salivary proline-rich protein 3 Human genes 0.000 description 2
- 102100021895 Bcl-2-like protein 13 Human genes 0.000 description 2
- 108091010858 Bcl-2-like protein 13 Proteins 0.000 description 2
- 102100022541 Bcl-2-related ovarian killer protein Human genes 0.000 description 2
- 101150042035 Bpifa1 gene Proteins 0.000 description 2
- 208000003174 Brain Neoplasms Diseases 0.000 description 2
- 101150058704 CD200R1 gene Proteins 0.000 description 2
- 102100036008 CD48 antigen Human genes 0.000 description 2
- 101100005878 Caenorhabditis elegans fmi-1 gene Proteins 0.000 description 2
- 101710147333 Calcineurin B homologous protein 2 Proteins 0.000 description 2
- 102100024316 Calcium/calmodulin-dependent 3',5'-cyclic nucleotide phosphodiesterase 1A Human genes 0.000 description 2
- 101710193674 Calcium/calmodulin-dependent protein kinase II inhibitor 1 Proteins 0.000 description 2
- 102100033093 Calcium/calmodulin-dependent protein kinase type II subunit alpha Human genes 0.000 description 2
- 102000000584 Calmodulin Human genes 0.000 description 2
- 108010041952 Calmodulin Proteins 0.000 description 2
- 102100025456 Calpain-11 Human genes 0.000 description 2
- 101710165505 Calpain-11 Proteins 0.000 description 2
- 101710113083 Carbamoyl-phosphate synthase Proteins 0.000 description 2
- 108010078791 Carrier Proteins Proteins 0.000 description 2
- 108010076667 Caspases Proteins 0.000 description 2
- 102000011727 Caspases Human genes 0.000 description 2
- 101710106615 Catenin alpha-1 Proteins 0.000 description 2
- 102000016362 Catenins Human genes 0.000 description 2
- 108010067316 Catenins Proteins 0.000 description 2
- 102100028013 Cation channel sperm-associated auxiliary subunit beta Human genes 0.000 description 2
- 102100028012 Cation channel sperm-associated auxiliary subunit delta Human genes 0.000 description 2
- 102100035696 Centrosome-associated protein 350 Human genes 0.000 description 2
- 101710101089 Centrosome-associated protein 350 Proteins 0.000 description 2
- 206010008342 Cervix carcinoma Diseases 0.000 description 2
- 102100039550 Chemokine-like factor Human genes 0.000 description 2
- 101710204213 Chemokine-like factor Proteins 0.000 description 2
- 102100023331 Cilia- and flagella-associated protein 43 Human genes 0.000 description 2
- 101710131331 Claudin domain-containing protein 1 Proteins 0.000 description 2
- 102100038449 Claudin-6 Human genes 0.000 description 2
- 108090000229 Claudin-6 Proteins 0.000 description 2
- 108010076130 Cleavage And Polyadenylation Specificity Factor Proteins 0.000 description 2
- 102100030954 Cleavage and polyadenylation specificity factor subunit 3 Human genes 0.000 description 2
- 102100037291 Coatomer subunit gamma-2 Human genes 0.000 description 2
- 101710155794 Coatomer subunit gamma-2 Proteins 0.000 description 2
- 102100035590 Cohesin subunit SA-1 Human genes 0.000 description 2
- 101710173923 Cohesin subunit SA-1 Proteins 0.000 description 2
- 102100023668 Coiled-coil domain-containing protein 122 Human genes 0.000 description 2
- 102100035164 Coiled-coil domain-containing protein 60 Human genes 0.000 description 2
- 102100023717 Coiled-coil domain-containing protein 77 Human genes 0.000 description 2
- 101710159592 Coiled-coil domain-containing protein 85B Proteins 0.000 description 2
- IVOMOUWHDPKRLL-KQYNXXCUSA-N Cyclic adenosine monophosphate Chemical compound C([C@H]1O2)OP(O)(=O)O[C@H]1[C@@H](O)[C@@H]2N1C(N=CN=C2N)=C2N=C1 IVOMOUWHDPKRLL-KQYNXXCUSA-N 0.000 description 2
- 102000008160 Cyclin A1 Human genes 0.000 description 2
- 108010060267 Cyclin A1 Proteins 0.000 description 2
- 101710106279 Cyclin-dependent kinase 1 Proteins 0.000 description 2
- 102100034976 Cystathionine beta-synthase Human genes 0.000 description 2
- 108010073644 Cystathionine beta-synthase Proteins 0.000 description 2
- 108010001202 Cytochrome P-450 CYP2E1 Proteins 0.000 description 2
- 102100038418 Cytoplasmic FMR1-interacting protein 2 Human genes 0.000 description 2
- 102100039224 Cytoplasmic polyadenylation element-binding protein 2 Human genes 0.000 description 2
- 102100037753 DEP domain-containing protein 1A Human genes 0.000 description 2
- 102100031867 DNA excision repair protein ERCC-6 Human genes 0.000 description 2
- 101710162619 DNA excision repair protein ERCC-6 Proteins 0.000 description 2
- 102100037700 DNA mismatch repair protein Msh3 Human genes 0.000 description 2
- 101710099953 DNA mismatch repair protein msh3 Proteins 0.000 description 2
- 101710118395 DNA repair protein RAD50 Proteins 0.000 description 2
- 102100033072 DNA replication ATP-dependent helicase DNA2 Human genes 0.000 description 2
- 101710162981 DNA replication ATP-dependent helicase DNA2 Proteins 0.000 description 2
- 102100027617 DNA/RNA-binding protein KIN17 Human genes 0.000 description 2
- 102100031598 Dedicator of cytokinesis protein 1 Human genes 0.000 description 2
- 101710113370 Dedicator of cytokinesis protein 1 Proteins 0.000 description 2
- 101710088194 Dehydrogenase Proteins 0.000 description 2
- 229920002307 Dextran Polymers 0.000 description 2
- 101001129775 Dictyostelium discoideum Sca1 complex protein phr Proteins 0.000 description 2
- 235000019005 Digitaria californica Nutrition 0.000 description 2
- 241001115843 Digitaria californica Species 0.000 description 2
- 102100031111 Disintegrin and metalloproteinase domain-containing protein 17 Human genes 0.000 description 2
- 102100031116 Disintegrin and metalloproteinase domain-containing protein 19 Human genes 0.000 description 2
- 101001108871 Drosophila melanogaster Nucleoporin Nup188 Proteins 0.000 description 2
- 101001081251 Drosophila melanogaster Protein held out wings Proteins 0.000 description 2
- 102100031636 Dynein axonemal heavy chain 9 Human genes 0.000 description 2
- 102100032249 Dystonin Human genes 0.000 description 2
- 108010013976 Dystonin Proteins 0.000 description 2
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 2
- 102100033905 EF-hand calcium-binding domain-containing protein 7 Human genes 0.000 description 2
- 101710043326 EMILIN-3 Proteins 0.000 description 2
- 241000258955 Echinodermata Species 0.000 description 2
- 101710199605 Endoribonuclease Proteins 0.000 description 2
- 102100032450 Endothelial differentiation-related factor 1 Human genes 0.000 description 2
- 101710182961 Endothelial differentiation-related factor 1 Proteins 0.000 description 2
- 101710159618 Endothelial differentiation-related factor 1 homolog Proteins 0.000 description 2
- 102100021805 Enhancer of mRNA-decapping protein 4 Human genes 0.000 description 2
- 102100032460 Ensconsin Human genes 0.000 description 2
- 101710082033 Ensconsin Proteins 0.000 description 2
- 102000004190 Enzymes Human genes 0.000 description 2
- 108090000790 Enzymes Proteins 0.000 description 2
- 108010007005 Estrogen Receptor alpha Proteins 0.000 description 2
- 102100038595 Estrogen receptor Human genes 0.000 description 2
- 102100035045 Eukaryotic translation initiation factor 3 subunit C Human genes 0.000 description 2
- 101710109030 Eukaryotic translation initiation factor 3 subunit C Proteins 0.000 description 2
- 102100029095 Exportin-1 Human genes 0.000 description 2
- 102100040650 F-BAR and double SH3 domains protein 2 Human genes 0.000 description 2
- 108010066805 F-Box Proteins Proteins 0.000 description 2
- 102000018700 F-Box Proteins Human genes 0.000 description 2
- 102100022113 F-box only protein 28 Human genes 0.000 description 2
- 101710190897 F-box only protein 28 Proteins 0.000 description 2
- 102100037338 F-box/LRR-repeat protein 5 Human genes 0.000 description 2
- 101710083634 F-box/LRR-repeat protein 5 Proteins 0.000 description 2
- 102100029327 FERM domain-containing protein 4A Human genes 0.000 description 2
- 101710193520 FERM domain-containing protein 4A Proteins 0.000 description 2
- 102100038516 FERM domain-containing protein 6 Human genes 0.000 description 2
- 101710196047 FERM domain-containing protein 6 Proteins 0.000 description 2
- 108010039471 Fas Ligand Protein Proteins 0.000 description 2
- 101000941893 Felis catus Leucine-rich repeat and calponin homology domain-containing protein 1 Proteins 0.000 description 2
- 102100040777 Fibrinogen C domain-containing protein 1 Human genes 0.000 description 2
- 108010068561 Fructose-Bisphosphate Aldolase Proteins 0.000 description 2
- 101710123709 Fructose-bisphosphate aldolase C Proteins 0.000 description 2
- 102000034286 G proteins Human genes 0.000 description 2
- 102000003688 G-Protein-Coupled Receptors Human genes 0.000 description 2
- 108090000045 G-Protein-Coupled Receptors Proteins 0.000 description 2
- 102100032524 G-protein coupled receptor family C group 5 member C Human genes 0.000 description 2
- 101710174801 G-protein coupled receptor family C group 5 member C Proteins 0.000 description 2
- 102000001411 G2 and S phase-expressed protein 1 Human genes 0.000 description 2
- 108050009617 G2 and S phase-expressed protein 1 Proteins 0.000 description 2
- 102000005915 GABA Receptors Human genes 0.000 description 2
- 108010005551 GABA Receptors Proteins 0.000 description 2
- 108090000839 GABA-A Receptors Proteins 0.000 description 2
- 102000004300 GABA-A Receptors Human genes 0.000 description 2
- 102100025477 GTP-binding protein Rit1 Human genes 0.000 description 2
- 101710196229 GTP-binding protein Rit1 Proteins 0.000 description 2
- 101710112780 Gene 1 protein Proteins 0.000 description 2
- 108700039691 Genetic Promoter Regions Proteins 0.000 description 2
- 102100037390 Genetic suppressor element 1 Human genes 0.000 description 2
- 102100039847 Globoside alpha-1,3-N-acetylgalactosaminyltransferase 1 Human genes 0.000 description 2
- 102000006395 Globulins Human genes 0.000 description 2
- 108010044091 Globulins Proteins 0.000 description 2
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 2
- 101710199506 Golgin subfamily B member 1 Proteins 0.000 description 2
- 101710202385 Growth hormone secretagogue receptor type 1 Proteins 0.000 description 2
- 102100034339 Guanine nucleotide-binding protein G(olf) subunit alpha Human genes 0.000 description 2
- 101710124329 Guanine nucleotide-binding protein G(olf) subunit alpha Proteins 0.000 description 2
- 102100028538 Guanylate-binding protein 4 Human genes 0.000 description 2
- 101710110797 Guanylate-binding protein 4 Proteins 0.000 description 2
- 108091008603 HGF receptors Proteins 0.000 description 2
- 102100028976 HLA class I histocompatibility antigen, B alpha chain Human genes 0.000 description 2
- 102100028971 HLA class I histocompatibility antigen, C alpha chain Human genes 0.000 description 2
- 102000011786 HLA-A Antigens Human genes 0.000 description 2
- 108010075704 HLA-A Antigens Proteins 0.000 description 2
- 108010058607 HLA-B Antigens Proteins 0.000 description 2
- 108010052199 HLA-C Antigens Proteins 0.000 description 2
- 102100034051 Heat shock protein HSP 90-alpha Human genes 0.000 description 2
- 101710147599 Heat shock protein HSP 90-alpha Proteins 0.000 description 2
- 102100039168 Heat shock protein beta-3 Human genes 0.000 description 2
- 102100037174 Helicase MOV-10 Human genes 0.000 description 2
- 102100029977 Helicase SKI2W Human genes 0.000 description 2
- 102100031019 Helicase with zinc finger domain 2 Human genes 0.000 description 2
- 102000002737 Heme Oxygenase-1 Human genes 0.000 description 2
- 229920002971 Heparan sulfate Polymers 0.000 description 2
- 102100023923 Heparan sulfate glucosamine 3-O-sulfotransferase 5 Human genes 0.000 description 2
- 102100031188 Hephaestin Human genes 0.000 description 2
- 108700038053 Hephaestin Proteins 0.000 description 2
- 102100028895 Heterogeneous nuclear ribonucleoprotein M Human genes 0.000 description 2
- 102100023999 Heterogeneous nuclear ribonucleoprotein R Human genes 0.000 description 2
- 108010042923 Heterogeneous-Nuclear Ribonucleoprotein Group M Proteins 0.000 description 2
- 108010036115 Histone Methyltransferases Proteins 0.000 description 2
- 102000011787 Histone Methyltransferases Human genes 0.000 description 2
- 102100029768 Histone-lysine N-methyltransferase SETD1A Human genes 0.000 description 2
- 108700005087 Homeobox Genes Proteins 0.000 description 2
- 102000009331 Homeodomain Proteins Human genes 0.000 description 2
- 108010048671 Homeodomain Proteins Proteins 0.000 description 2
- 101000597332 Homo sapiens 2'-5'-oligoadenylate synthase 3 Proteins 0.000 description 2
- 101000823289 Homo sapiens ATP-binding cassette sub-family F member 2 Proteins 0.000 description 2
- 101000901109 Homo sapiens Achaete-scute homolog 2 Proteins 0.000 description 2
- 101000690901 Homo sapiens Activity-dependent neuroprotector homeobox protein 2 Proteins 0.000 description 2
- 101001062620 Homo sapiens Alpha-ketoglutarate-dependent dioxygenase FTO Proteins 0.000 description 2
- 101000757194 Homo sapiens Ankyrin repeat domain-containing protein 18B Proteins 0.000 description 2
- 101000793444 Homo sapiens Apolipoprotein L4 Proteins 0.000 description 2
- 101000803294 Homo sapiens BCL2/adenovirus E1B 19 kDa protein-interacting protein 3 Proteins 0.000 description 2
- 101000697486 Homo sapiens BRCA1-associated RING domain protein 1 Proteins 0.000 description 2
- 101000697669 Homo sapiens Bardet-Biedl syndrome 7 protein Proteins 0.000 description 2
- 101001068638 Homo sapiens Basic salivary proline-rich protein 3 Proteins 0.000 description 2
- 101000899346 Homo sapiens Bcl-2-related ovarian killer protein Proteins 0.000 description 2
- 101001094636 Homo sapiens Blood vessel epicardial substance Proteins 0.000 description 2
- 101000715671 Homo sapiens Cadherin EGF LAG seven-pass G-type receptor 3 Proteins 0.000 description 2
- 101000859040 Homo sapiens Cation channel sperm-associated auxiliary subunit beta Proteins 0.000 description 2
- 101000859043 Homo sapiens Cation channel sperm-associated auxiliary subunit delta Proteins 0.000 description 2
- 101001130422 Homo sapiens Cell cycle checkpoint protein RAD17 Proteins 0.000 description 2
- 101000944434 Homo sapiens Centrosomal protein of 70 kDa Proteins 0.000 description 2
- 101000907999 Homo sapiens Cilia- and flagella-associated protein 43 Proteins 0.000 description 2
- 101000912657 Homo sapiens Claudin domain-containing protein 1 Proteins 0.000 description 2
- 101000911390 Homo sapiens Coagulation factor VIII Proteins 0.000 description 2
- 101000978258 Homo sapiens Coiled-coil domain-containing protein 122 Proteins 0.000 description 2
- 101000737071 Homo sapiens Coiled-coil domain-containing protein 60 Proteins 0.000 description 2
- 101000978318 Homo sapiens Coiled-coil domain-containing protein 77 Proteins 0.000 description 2
- 101000868814 Homo sapiens Coiled-coil domain-containing protein 85B Proteins 0.000 description 2
- 101000956870 Homo sapiens Cytoplasmic FMR1-interacting protein 2 Proteins 0.000 description 2
- 101000745751 Homo sapiens Cytoplasmic polyadenylation element-binding protein 2 Proteins 0.000 description 2
- 101000950642 Homo sapiens DEP domain-containing protein 1A Proteins 0.000 description 2
- 101000743929 Homo sapiens DNA repair protein RAD50 Proteins 0.000 description 2
- 101001008941 Homo sapiens DNA/RNA-binding protein KIN17 Proteins 0.000 description 2
- 101000777464 Homo sapiens Disintegrin and metalloproteinase domain-containing protein 19 Proteins 0.000 description 2
- 101000866325 Homo sapiens Dynein axonemal heavy chain 9 Proteins 0.000 description 2
- 101000925424 Homo sapiens EF-hand calcium-binding domain-containing protein 7 Proteins 0.000 description 2
- 101000921276 Homo sapiens EMILIN-3 Proteins 0.000 description 2
- 101000588298 Homo sapiens Endoplasmic reticulum membrane sensor NFE2L1 Proteins 0.000 description 2
- 101000895665 Homo sapiens Enhancer of mRNA-decapping protein 4 Proteins 0.000 description 2
- 101000892420 Homo sapiens F-BAR and double SH3 domains protein 2 Proteins 0.000 description 2
- 101001026867 Homo sapiens F-box/LRR-repeat protein 4 Proteins 0.000 description 2
- 101001026853 Homo sapiens F-box/LRR-repeat protein 5 Proteins 0.000 description 2
- 101000892088 Homo sapiens Fibrinogen C domain-containing protein 1 Proteins 0.000 description 2
- 101001026271 Homo sapiens Genetic suppressor element 1 Proteins 0.000 description 2
- 101000887519 Homo sapiens Globoside alpha-1,3-N-acetylgalactosaminyltransferase 1 Proteins 0.000 description 2
- 101000746373 Homo sapiens Granulocyte-macrophage colony-stimulating factor Proteins 0.000 description 2
- 101001036701 Homo sapiens Heat shock protein beta-3 Proteins 0.000 description 2
- 101001028696 Homo sapiens Helicase MOV-10 Proteins 0.000 description 2
- 101000863680 Homo sapiens Helicase SKI2W Proteins 0.000 description 2
- 101001083766 Homo sapiens Helicase with zinc finger domain 2 Proteins 0.000 description 2
- 101000972946 Homo sapiens Hepatocyte growth factor receptor Proteins 0.000 description 2
- 101001081151 Homo sapiens Heterogeneous nuclear ribonucleoprotein C-like 1 Proteins 0.000 description 2
- 101001047853 Homo sapiens Heterogeneous nuclear ribonucleoprotein R Proteins 0.000 description 2
- 101001082500 Homo sapiens Histatin-1 Proteins 0.000 description 2
- 101000865038 Homo sapiens Histone-lysine N-methyltransferase SETD1A Proteins 0.000 description 2
- 101000953492 Homo sapiens Inositol hexakisphosphate and diphosphoinositol-pentakisphosphate kinase 1 Proteins 0.000 description 2
- 101001002657 Homo sapiens Interleukin-2 Proteins 0.000 description 2
- 101001112162 Homo sapiens Kinetochore protein NDC80 homolog Proteins 0.000 description 2
- 101001037999 Homo sapiens LON peptidase N-terminal domain and RING finger protein 1 Proteins 0.000 description 2
- 101000605021 Homo sapiens Large neutral amino acids transporter small subunit 2 Proteins 0.000 description 2
- 101001017764 Homo sapiens Lipopolysaccharide-responsive and beige-like anchor protein Proteins 0.000 description 2
- 101000614020 Homo sapiens Lysine-specific demethylase 3B Proteins 0.000 description 2
- 101000957335 Homo sapiens Lysophospholipid acyltransferase 1 Proteins 0.000 description 2
- 101000578951 Homo sapiens MAP7 domain-containing protein 2 Proteins 0.000 description 2
- 101000756759 Homo sapiens MHC class II regulatory factor RFX1 Proteins 0.000 description 2
- 101000969827 Homo sapiens Maestro heat-like repeat-containing protein family member 1 Proteins 0.000 description 2
- 101000937642 Homo sapiens Malonyl-CoA-acyl carrier protein transacylase, mitochondrial Proteins 0.000 description 2
- 101001095088 Homo sapiens Melanoma antigen preferentially expressed in tumors Proteins 0.000 description 2
- 101000993450 Homo sapiens Metal transporter CNNM3 Proteins 0.000 description 2
- 101001018298 Homo sapiens Microtubule-associated serine/threonine-protein kinase 4 Proteins 0.000 description 2
- 101000590830 Homo sapiens Monocarboxylate transporter 1 Proteins 0.000 description 2
- 101000958744 Homo sapiens Myosin-7B Proteins 0.000 description 2
- 101100186929 Homo sapiens NFE2L1 gene Proteins 0.000 description 2
- 101001112222 Homo sapiens Neural cell adhesion molecule L1-like protein Proteins 0.000 description 2
- 101001024613 Homo sapiens Neuroblastoma breakpoint family member 4 Proteins 0.000 description 2
- 101000577163 Homo sapiens Neurogenic locus notch homolog protein 4 Proteins 0.000 description 2
- 101001024605 Homo sapiens Next to BRCA1 gene 1 protein Proteins 0.000 description 2
- 101000721835 Homo sapiens Nuclear pore complex protein Nup98-Nup96 Proteins 0.000 description 2
- 101001108862 Homo sapiens Nucleoporin NUP188 Proteins 0.000 description 2
- 101001120706 Homo sapiens Outer dense fiber protein 2 Proteins 0.000 description 2
- 101001126471 Homo sapiens Plectin Proteins 0.000 description 2
- 101001067189 Homo sapiens Plexin-A1 Proteins 0.000 description 2
- 101001067174 Homo sapiens Plexin-B1 Proteins 0.000 description 2
- 101000952113 Homo sapiens Probable ATP-dependent RNA helicase DDX5 Proteins 0.000 description 2
- 101000872867 Homo sapiens Probable E3 ubiquitin-protein ligase HECTD4 Proteins 0.000 description 2
- 101001123492 Homo sapiens Prolactin-releasing peptide receptor Proteins 0.000 description 2
- 101000933604 Homo sapiens Protein BTG2 Proteins 0.000 description 2
- 101000817237 Homo sapiens Protein ECT2 Proteins 0.000 description 2
- 101001048933 Homo sapiens Protein FAM187B Proteins 0.000 description 2
- 101001021281 Homo sapiens Protein HEXIM1 Proteins 0.000 description 2
- 101000979460 Homo sapiens Protein Niban 1 Proteins 0.000 description 2
- 101001072579 Homo sapiens Protein PAXX Proteins 0.000 description 2
- 101001068634 Homo sapiens Protein PRRC2A Proteins 0.000 description 2
- 101000595876 Homo sapiens Protein TASOR Proteins 0.000 description 2
- 101000747057 Homo sapiens Protein YIF1B Proteins 0.000 description 2
- 101001000956 Homo sapiens Protein fuzzy homolog Proteins 0.000 description 2
- 101000760449 Homo sapiens Protein unc-93 homolog B1 Proteins 0.000 description 2
- 101001050438 Homo sapiens Protein-lysine N-methyltransferase EEF2KMT Proteins 0.000 description 2
- 101000859669 Homo sapiens Putative ciliary rootlet coiled-coil protein-like 2 protein Proteins 0.000 description 2
- 101000734537 Homo sapiens Pyridoxal-dependent decarboxylase domain-containing protein 1 Proteins 0.000 description 2
- 101000927086 Homo sapiens RNA helicase aquarius Proteins 0.000 description 2
- 101000694402 Homo sapiens RNA transcription, translation and transport factor protein Proteins 0.000 description 2
- 101000580716 Homo sapiens RNA-binding protein 24 Proteins 0.000 description 2
- 101001076728 Homo sapiens RNA-binding protein 34 Proteins 0.000 description 2
- 101000713960 Homo sapiens RUN and FYVE domain-containing protein 2 Proteins 0.000 description 2
- 101001061807 Homo sapiens Rab-like protein 6 Proteins 0.000 description 2
- 101000703428 Homo sapiens Rho GTPase-activating protein 36 Proteins 0.000 description 2
- 101000703425 Homo sapiens Rho GTPase-activating protein 39 Proteins 0.000 description 2
- 101001106322 Homo sapiens Rho GTPase-activating protein 7 Proteins 0.000 description 2
- 101000704874 Homo sapiens Rho family-interacting cell polarization regulator 2 Proteins 0.000 description 2
- 101000659995 Homo sapiens Ribosomal L1 domain-containing protein 1 Proteins 0.000 description 2
- 101000703089 Homo sapiens Set1/Ash2 histone methyltransferase complex subunit ASH2 Proteins 0.000 description 2
- 101000703745 Homo sapiens Shootin-1 Proteins 0.000 description 2
- 101000618118 Homo sapiens Speriolin-like protein Proteins 0.000 description 2
- 101000618133 Homo sapiens Sperm-associated antigen 5 Proteins 0.000 description 2
- 101000674440 Homo sapiens Synaptopodin 2-like protein Proteins 0.000 description 2
- 101000595764 Homo sapiens TBC1 domain family member 9B Proteins 0.000 description 2
- 101000648827 Homo sapiens TPR and ankyrin repeat-containing protein 1 Proteins 0.000 description 2
- 101000596268 Homo sapiens Taste receptor type 2 member 40 Proteins 0.000 description 2
- 101000626153 Homo sapiens Tensin-3 Proteins 0.000 description 2
- 101000633680 Homo sapiens Tetratricopeptide repeat protein 37 Proteins 0.000 description 2
- 101000866298 Homo sapiens Transcription factor E2F8 Proteins 0.000 description 2
- 101000904724 Homo sapiens Transmembrane glycoprotein NMB Proteins 0.000 description 2
- 101000598045 Homo sapiens Transmembrane protein 115 Proteins 0.000 description 2
- 101000640731 Homo sapiens Transmembrane protein 132B Proteins 0.000 description 2
- 101000640976 Homo sapiens Tryptophan-tRNA ligase, cytoplasmic Proteins 0.000 description 2
- 101000800807 Homo sapiens Tumor necrosis factor alpha-induced protein 8 Proteins 0.000 description 2
- 101000638161 Homo sapiens Tumor necrosis factor ligand superfamily member 6 Proteins 0.000 description 2
- 101000762128 Homo sapiens Tumor suppressor candidate 3 Proteins 0.000 description 2
- 101000697888 Homo sapiens UDP-GalNAc:beta-1,3-N-acetylgalactosaminyltransferase 2 Proteins 0.000 description 2
- 101000607643 Homo sapiens Ubiquilin-like protein Proteins 0.000 description 2
- 101000772888 Homo sapiens Ubiquitin-protein ligase E3A Proteins 0.000 description 2
- 101000982047 Homo sapiens Unconventional myosin-XIX Proteins 0.000 description 2
- 101000767597 Homo sapiens Vascular endothelial zinc finger 1 Proteins 0.000 description 2
- 101000932804 Homo sapiens Voltage-dependent T-type calcium channel subunit alpha-1H Proteins 0.000 description 2
- 101000743114 Homo sapiens WASH complex subunit 4 Proteins 0.000 description 2
- 101100321634 Homo sapiens ZYG11B gene Proteins 0.000 description 2
- 101000802413 Homo sapiens Zinc finger protein 770 Proteins 0.000 description 2
- 101000976393 Homo sapiens Zyxin Proteins 0.000 description 2
- 108010044240 IFIH1 Interferon-Induced Helicase Proteins 0.000 description 2
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 2
- 108060003951 Immunoglobulin Proteins 0.000 description 2
- 102100021033 Immunoglobulin superfamily member 10 Human genes 0.000 description 2
- 101710115889 Immunoglobulin superfamily member 10 Proteins 0.000 description 2
- 102100024070 Inhibitor of growth protein 3 Human genes 0.000 description 2
- 108700038214 Inhibitor of growth protein 3 Proteins 0.000 description 2
- 102100037739 Inositol hexakisphosphate and diphosphoinositol-pentakisphosphate kinase 1 Human genes 0.000 description 2
- 102100024367 Inositol polyphosphate-4-phosphatase type I A Human genes 0.000 description 2
- 101710148446 Inositol-trisphosphate 3-kinase B Proteins 0.000 description 2
- 102000003746 Insulin Receptor Human genes 0.000 description 2
- 108010001127 Insulin Receptor Proteins 0.000 description 2
- 102100033000 Integrin beta-4 Human genes 0.000 description 2
- 108010078049 Interferon alpha-2 Proteins 0.000 description 2
- 102100039350 Interferon alpha-7 Human genes 0.000 description 2
- 102100037850 Interferon gamma Human genes 0.000 description 2
- 102100027353 Interferon-induced helicase C domain-containing protein 1 Human genes 0.000 description 2
- 108010002352 Interleukin-1 Proteins 0.000 description 2
- 102000000589 Interleukin-1 Human genes 0.000 description 2
- 102100030692 Interleukin-20 Human genes 0.000 description 2
- 101710015718 KIAA0100 Proteins 0.000 description 2
- 102100032704 Keratin, type I cytoskeletal 24 Human genes 0.000 description 2
- 101710183646 Keratin, type I cytoskeletal 24 Proteins 0.000 description 2
- 102100023972 Keratin, type II cytoskeletal 8 Human genes 0.000 description 2
- 101710194927 Keratin, type II cytoskeletal 8 Proteins 0.000 description 2
- 101710104293 KiSS-1 receptor Proteins 0.000 description 2
- 108050001953 Kinesin-like protein KIF13A Proteins 0.000 description 2
- 102100023890 Kinetochore protein NDC80 homolog Human genes 0.000 description 2
- QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 description 2
- 150000008575 L-amino acids Chemical class 0.000 description 2
- ROHFNLRQFUQHCH-YFKPBYRVSA-N L-leucine Chemical compound CC(C)C[C@H](N)C(O)=O ROHFNLRQFUQHCH-YFKPBYRVSA-N 0.000 description 2
- 102000007330 LDL Lipoproteins Human genes 0.000 description 2
- 108010007622 LDL Lipoproteins Proteins 0.000 description 2
- 108010001831 LDL receptors Proteins 0.000 description 2
- 102100040390 LON peptidase N-terminal domain and RING finger protein 1 Human genes 0.000 description 2
- ROHFNLRQFUQHCH-UHFFFAOYSA-N Leucine Natural products CC(C)CC(N)C(O)=O ROHFNLRQFUQHCH-UHFFFAOYSA-N 0.000 description 2
- 101710174256 Leucine-rich repeat-containing G-protein coupled receptor 5 Proteins 0.000 description 2
- 102100033353 Lipopolysaccharide-responsive and beige-like anchor protein Human genes 0.000 description 2
- 102000001851 Low Density Lipoprotein Receptor-Related Protein-1 Human genes 0.000 description 2
- 108010015340 Low Density Lipoprotein Receptor-Related Protein-1 Proteins 0.000 description 2
- 102100024640 Low-density lipoprotein receptor Human genes 0.000 description 2
- 102100040582 Lysine-specific demethylase 3B Human genes 0.000 description 2
- 101710105716 Lysine-specific demethylase 5A Proteins 0.000 description 2
- 102100038754 Lysophospholipid acyltransferase 1 Human genes 0.000 description 2
- 102100028240 MAP7 domain-containing protein 2 Human genes 0.000 description 2
- 108700012928 MAPK14 Proteins 0.000 description 2
- 102000019867 MKL/myocardin-like protein 1 Human genes 0.000 description 2
- 108091016358 MKL/myocardin-like protein 1 Proteins 0.000 description 2
- 241000282567 Macaca fascicularis Species 0.000 description 2
- 102100021343 Maestro heat-like repeat-containing protein family member 1 Human genes 0.000 description 2
- 101710120903 Malignant T-cell-amplified sequence 1 Proteins 0.000 description 2
- 241000124008 Mammalia Species 0.000 description 2
- 102100024132 Matrix metalloproteinase-27 Human genes 0.000 description 2
- 108050005201 Matrix metalloproteinase-27 Proteins 0.000 description 2
- 101710179434 Mediator of RNA polymerase II transcription subunit 23 Proteins 0.000 description 2
- 102100037020 Melanoma antigen preferentially expressed in tumors Human genes 0.000 description 2
- 102000000440 Melanoma-associated antigen Human genes 0.000 description 2
- 108050008953 Melanoma-associated antigen Proteins 0.000 description 2
- 108050007204 Melanoma-associated antigen D2 Proteins 0.000 description 2
- 101710178869 Melanoma-associated antigen E2 Proteins 0.000 description 2
- 102000015941 Member 1 Group C Nuclear Receptor Subfamily 2 Human genes 0.000 description 2
- 102000018697 Membrane Proteins Human genes 0.000 description 2
- 108010052285 Membrane Proteins Proteins 0.000 description 2
- 102100031678 Metal transporter CNNM3 Human genes 0.000 description 2
- 102100033252 Microtubule-associated serine/threonine-protein kinase 4 Human genes 0.000 description 2
- 108010042046 Mitochondrial processing peptidase Proteins 0.000 description 2
- 102100023482 Mitogen-activated protein kinase 14 Human genes 0.000 description 2
- 102100025211 Mitogen-activated protein kinase kinase kinase 14 Human genes 0.000 description 2
- 102100028192 Mitogen-activated protein kinase kinase kinase kinase 2 Human genes 0.000 description 2
- 101710144533 Mitogen-activated protein kinase kinase kinase kinase 2 Proteins 0.000 description 2
- 101000697670 Mus musculus Bardet-Biedl syndrome 7 protein homolog Proteins 0.000 description 2
- 101000921277 Mus musculus EMILIN-3 Proteins 0.000 description 2
- 101001126472 Mus musculus Plectin Proteins 0.000 description 2
- 101001028698 Mus musculus Putative helicase MOV-10 Proteins 0.000 description 2
- 102100026786 Myopalladin Human genes 0.000 description 2
- 101710189520 Myopalladin Proteins 0.000 description 2
- 101710089434 Myosin heavy chain, non-muscle Proteins 0.000 description 2
- 102100036640 Myosin-10 Human genes 0.000 description 2
- 101710115163 Myosin-10 Proteins 0.000 description 2
- 102100038934 Myosin-7 Human genes 0.000 description 2
- 101710204029 Myosin-7 Proteins 0.000 description 2
- 102100038322 Myosin-7B Human genes 0.000 description 2
- OVRNDRQMDRJTHS-FMDGEEDCSA-N N-acetyl-beta-D-glucosamine Chemical compound CC(=O)N[C@H]1[C@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O OVRNDRQMDRJTHS-FMDGEEDCSA-N 0.000 description 2
- 108010018525 NFATC Transcription Factors Proteins 0.000 description 2
- 102000002673 NFATC Transcription Factors Human genes 0.000 description 2
- 102100036942 Nck-associated protein 1-like Human genes 0.000 description 2
- 101710199621 Nck-associated protein 1-like Proteins 0.000 description 2
- 102100028803 Nebulin-related-anchoring protein Human genes 0.000 description 2
- 101710187057 Nebulin-related-anchoring protein Proteins 0.000 description 2
- 101710115202 Netrin receptor DCC Proteins 0.000 description 2
- 108010069196 Neural Cell Adhesion Molecules Proteins 0.000 description 2
- 102100027347 Neural cell adhesion molecule 1 Human genes 0.000 description 2
- 108050003738 Neural cell adhesion molecule 1 Proteins 0.000 description 2
- 102100023616 Neural cell adhesion molecule L1-like protein Human genes 0.000 description 2
- 102100037015 Neuroblastoma breakpoint family member 4 Human genes 0.000 description 2
- 101100217524 Neurospora crassa (strain ATCC 24698 / 74-OR23-1A / CBS 708.71 / DSM 1257 / FGSC 987) apg-1 gene Proteins 0.000 description 2
- 102100035107 Neurotrimin Human genes 0.000 description 2
- 102100036592 Neutral alpha-glucosidase AB Human genes 0.000 description 2
- 101710140639 Neutral alpha-glucosidase AB Proteins 0.000 description 2
- 102100038995 Nischarin Human genes 0.000 description 2
- 101710085246 Nischarin Proteins 0.000 description 2
- 101710089543 Nitric oxide synthase, inducible Proteins 0.000 description 2
- 208000015914 Non-Hodgkin lymphomas Diseases 0.000 description 2
- 101800000613 Notch 1 extracellular truncation Proteins 0.000 description 2
- 102400000553 Notch 1 extracellular truncation Human genes 0.000 description 2
- 101800001628 Notch 1 intracellular domain Proteins 0.000 description 2
- 102400000552 Notch 1 intracellular domain Human genes 0.000 description 2
- 101800000274 Notch 3 extracellular truncation Proteins 0.000 description 2
- 102400000548 Notch 3 extracellular truncation Human genes 0.000 description 2
- 101800000993 Notch 3 intracellular domain Proteins 0.000 description 2
- 102400000547 Notch 3 intracellular domain Human genes 0.000 description 2
- 101800001130 Notch 4 extracellular truncation Proteins 0.000 description 2
- 102400000543 Notch 4 extracellular truncation Human genes 0.000 description 2
- 101800000017 Notch 4 intracellular domain Proteins 0.000 description 2
- 102400000544 Notch 4 intracellular domain Human genes 0.000 description 2
- 108010029741 Notch4 Receptor Proteins 0.000 description 2
- 102100034404 Nuclear factor of activated T-cells, cytoplasmic 1 Human genes 0.000 description 2
- 101710151542 Nuclear factor of activated T-cells, cytoplasmic 1 Proteins 0.000 description 2
- 102100021530 Nucleoporin NUP188 Human genes 0.000 description 2
- 102100033615 Nucleoprotein TPR Human genes 0.000 description 2
- 101710145115 Nucleoprotein TPR Proteins 0.000 description 2
- 101150088426 Nup107 gene Proteins 0.000 description 2
- 108050000742 Orexin Receptor Proteins 0.000 description 2
- 102000008834 Orexin receptor Human genes 0.000 description 2
- 102100026069 Outer dense fiber protein 2 Human genes 0.000 description 2
- 102100027952 Oxidoreductase HTATIP2 Human genes 0.000 description 2
- 101710137390 P-selectin glycoprotein ligand 1 Proteins 0.000 description 2
- 108010054395 P-selectin ligand protein Proteins 0.000 description 2
- 102000000470 PDZ domains Human genes 0.000 description 2
- 108050008994 PDZ domains Proteins 0.000 description 2
- 101710115894 Pecanex-like protein 1 Proteins 0.000 description 2
- 102100036983 Peptidyl-prolyl cis-trans isomerase FKBP7 Human genes 0.000 description 2
- 101710147138 Peptidyl-prolyl cis-trans isomerase FKBP7 Proteins 0.000 description 2
- 102100025058 Phosphatidylinositol 4-phosphate 3-kinase C2 domain-containing subunit alpha Human genes 0.000 description 2
- 102100026481 Phosphoinositide 3-kinase regulatory subunit 4 Human genes 0.000 description 2
- 102100030622 Phospholipid-transporting ATPase IA Human genes 0.000 description 2
- 101710135651 Phospholipid-transporting ATPase IA Proteins 0.000 description 2
- 108010057275 Plakophilins Proteins 0.000 description 2
- 102000003753 Plakophilins Human genes 0.000 description 2
- 102100035220 Plastin-3 Human genes 0.000 description 2
- 102100035968 Pleiotropic regulator 1 Human genes 0.000 description 2
- 101710178475 Pleiotropic regulator 1 Proteins 0.000 description 2
- 101710100257 Plexin-A1 Proteins 0.000 description 2
- 102100034384 Plexin-B1 Human genes 0.000 description 2
- 101710100551 Plexin-B2 Proteins 0.000 description 2
- 102100033237 Pro-epidermal growth factor Human genes 0.000 description 2
- 102100033405 Probable ATP-dependent RNA helicase DDX27 Human genes 0.000 description 2
- 102100037434 Probable ATP-dependent RNA helicase DDX5 Human genes 0.000 description 2
- 102100034679 Probable E3 ubiquitin-protein ligase HECTD4 Human genes 0.000 description 2
- 102000011195 Profilin Human genes 0.000 description 2
- 108050001408 Profilin Proteins 0.000 description 2
- 101710089364 Programmed cell death protein 5 Proteins 0.000 description 2
- 102000056271 Prolactin-releasing peptide receptors Human genes 0.000 description 2
- 101710084323 Prolyl 4-hydroxylase subunit alpha-1 Proteins 0.000 description 2
- 102100039025 Propionyl-CoA carboxylase beta chain, mitochondrial Human genes 0.000 description 2
- 101800001072 Protein 1A Proteins 0.000 description 2
- 102000006010 Protein Disulfide-Isomerase Human genes 0.000 description 2
- 102100040437 Protein ECT2 Human genes 0.000 description 2
- 102100023839 Protein FAM187B Human genes 0.000 description 2
- 102100036307 Protein HEXIM1 Human genes 0.000 description 2
- 102100037163 Protein KIAA0100 Human genes 0.000 description 2
- 102100023076 Protein Niban 1 Human genes 0.000 description 2
- 102100036663 Protein PAXX Human genes 0.000 description 2
- 101710130886 Protein PRRC2A Proteins 0.000 description 2
- 102100035191 Protein TASOR Human genes 0.000 description 2
- 101800000442 Protein X2 Proteins 0.000 description 2
- 102100039144 Protein YIF1B Human genes 0.000 description 2
- 102100037061 Protein disulfide-isomerase A6 Human genes 0.000 description 2
- 101710106306 Protein disulfide-isomerase A6 Proteins 0.000 description 2
- 102100040923 Protein flightless-1 homolog Human genes 0.000 description 2
- 101710203927 Protein flightless-1 homolog Proteins 0.000 description 2
- 102100035618 Protein fuzzy homolog Human genes 0.000 description 2
- 102100039154 Protein piccolo Human genes 0.000 description 2
- 101710140996 Protein piccolo Proteins 0.000 description 2
- 102100023366 Protein transport protein Sec23B Human genes 0.000 description 2
- 101710198443 Protein transport protein Sec23B Proteins 0.000 description 2
- 102100024740 Protein unc-93 homolog B1 Human genes 0.000 description 2
- 102100020908 Protein zyg-11 homolog B Human genes 0.000 description 2
- 102100023369 Protein-lysine N-methyltransferase EEF2KMT Human genes 0.000 description 2
- 102100036386 Protocadherin-10 Human genes 0.000 description 2
- 101710158923 Protocadherin-10 Proteins 0.000 description 2
- 102100027815 Putative ciliary rootlet coiled-coil protein-like 2 protein Human genes 0.000 description 2
- 101710096925 Putative helicase MOV-10 Proteins 0.000 description 2
- 102100034759 Pyridoxal-dependent decarboxylase domain-containing protein 1 Human genes 0.000 description 2
- LCTONWCANYUPML-UHFFFAOYSA-M Pyruvate Chemical compound CC(=O)C([O-])=O LCTONWCANYUPML-UHFFFAOYSA-M 0.000 description 2
- 102100033483 RNA helicase aquarius Human genes 0.000 description 2
- 102100027122 RNA transcription, translation and transport factor protein Human genes 0.000 description 2
- 102000044126 RNA-Binding Proteins Human genes 0.000 description 2
- 101710105008 RNA-binding protein Proteins 0.000 description 2
- 102100027487 RNA-binding protein 24 Human genes 0.000 description 2
- 101710133275 RNA-binding protein 6 Proteins 0.000 description 2
- 239000012980 RPMI-1640 medium Substances 0.000 description 2
- 102100036453 RUN and FYVE domain-containing protein 2 Human genes 0.000 description 2
- 102100029618 Rab-like protein 6 Human genes 0.000 description 2
- 102100039767 Ras-related protein Rab-27A Human genes 0.000 description 2
- 241000700157 Rattus norvegicus Species 0.000 description 2
- 101100163890 Rattus norvegicus Ascl2 gene Proteins 0.000 description 2
- 101100140980 Rattus norvegicus Dlc1 gene Proteins 0.000 description 2
- 108020004511 Recombinant DNA Proteins 0.000 description 2
- 201000000582 Retinoblastoma Diseases 0.000 description 2
- 108010071010 Retinoblastoma-Binding Protein 2 Proteins 0.000 description 2
- 102100022828 Retinoblastoma-like protein 2 Human genes 0.000 description 2
- 108050002651 Retinoblastoma-like protein 2 Proteins 0.000 description 2
- 102100030752 Rho GTPase-activating protein 36 Human genes 0.000 description 2
- 102100030748 Rho GTPase-activating protein 39 Human genes 0.000 description 2
- 102000016218 Rho GTPase-activating protein 6 Human genes 0.000 description 2
- 108050004712 Rho GTPase-activating protein 6 Proteins 0.000 description 2
- 101710116900 Rho GTPase-activating protein 7 Proteins 0.000 description 2
- 102100032023 Rho family-interacting cell polarization regulator 2 Human genes 0.000 description 2
- 102000003661 Ribonuclease III Human genes 0.000 description 2
- 108010057163 Ribonuclease III Proteins 0.000 description 2
- 102100027488 Roundabout homolog 3 Human genes 0.000 description 2
- 102100027092 RuvB-like 2 Human genes 0.000 description 2
- 101710111831 RuvB-like 2 Proteins 0.000 description 2
- 102100032121 Ryanodine receptor 2 Human genes 0.000 description 2
- 102100025487 S-phase kinase-associated protein 1 Human genes 0.000 description 2
- 108091007603 SLC58A2 Proteins 0.000 description 2
- 108091006238 SLC7A8 Proteins 0.000 description 2
- 108010044012 STAT1 Transcription Factor Proteins 0.000 description 2
- 229920002684 Sepharose Polymers 0.000 description 2
- 101710113029 Serine/threonine-protein kinase Proteins 0.000 description 2
- 101710094240 Set1/Ash2 histone methyltransferase complex subunit ASH2 Proteins 0.000 description 2
- 102100031975 Shootin-1 Human genes 0.000 description 2
- 102100029904 Signal transducer and activator of transcription 1-alpha/beta Human genes 0.000 description 2
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
- 102100027340 Slit homolog 2 protein Human genes 0.000 description 2
- 101710133576 Slit homolog 2 protein Proteins 0.000 description 2
- PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 description 2
- 108010019965 Spectrin Proteins 0.000 description 2
- 102000005890 Spectrin Human genes 0.000 description 2
- 102100021914 Speriolin-like protein Human genes 0.000 description 2
- 108091013841 Spermatogenesis-associated protein 6 Proteins 0.000 description 2
- 102100030257 Spermatogenesis-associated protein 7 Human genes 0.000 description 2
- 102100027662 Sphingosine kinase 2 Human genes 0.000 description 2
- 101710156532 Sphingosine kinase 2 Proteins 0.000 description 2
- 101000677856 Stenotrophomonas maltophilia (strain K279a) Actin-binding protein Smlt3054 Proteins 0.000 description 2
- 102100031797 Sulfiredoxin-1 Human genes 0.000 description 2
- 102100035581 Synaptojanin-2-binding protein Human genes 0.000 description 2
- 101710155018 Synaptojanin-2-binding protein Proteins 0.000 description 2
- 102100040469 Synaptopodin 2-like protein Human genes 0.000 description 2
- 101710084770 T-complex protein 1 subunit zeta 2 Proteins 0.000 description 2
- 102100030665 T-complex protein 1 subunit zeta-2 Human genes 0.000 description 2
- 108700026226 TATA Box Proteins 0.000 description 2
- 102100036069 TBC1 domain family member 9B Human genes 0.000 description 2
- 102100028173 TPR and ankyrin repeat-containing protein 1 Human genes 0.000 description 2
- 101710150687 Telomerase-binding protein EST1A Proteins 0.000 description 2
- 102100024548 Tensin-3 Human genes 0.000 description 2
- 102100034938 Terminal nucleotidyltransferase 4B Human genes 0.000 description 2
- 108700038060 Terminal nucleotidyltransferase 4B Proteins 0.000 description 2
- 102100031472 Tetratricopeptide repeat protein 17 Human genes 0.000 description 2
- 101710129158 Tetratricopeptide repeat protein 17 Proteins 0.000 description 2
- 102100029210 Tetratricopeptide repeat protein 37 Human genes 0.000 description 2
- 108010060752 Toll-Like Receptor 8 Proteins 0.000 description 2
- 102100033110 Toll-like receptor 8 Human genes 0.000 description 2
- 102100037451 Trafficking protein particle complex subunit 12 Human genes 0.000 description 2
- 101710105954 Trafficking protein particle complex subunit 12 Proteins 0.000 description 2
- 108010057666 Transcription Factor CHOP Proteins 0.000 description 2
- 102100031555 Transcription factor E2F8 Human genes 0.000 description 2
- 102100022446 Transcription factor Sp4 Human genes 0.000 description 2
- 102100024180 Transmembrane emp24 domain-containing protein 10 Human genes 0.000 description 2
- 101710188425 Transmembrane emp24 domain-containing protein 10 Proteins 0.000 description 2
- 102100023935 Transmembrane glycoprotein NMB Human genes 0.000 description 2
- 101710170975 Transmembrane protein 115 Proteins 0.000 description 2
- 102100033854 Transmembrane protein 132B Human genes 0.000 description 2
- 102100032250 Trichohyalin Human genes 0.000 description 2
- 108090000631 Trypsin Proteins 0.000 description 2
- 102000004142 Trypsin Human genes 0.000 description 2
- 102000002501 Tryptophan-tRNA Ligase Human genes 0.000 description 2
- 108700025716 Tumor Suppressor Genes Proteins 0.000 description 2
- 102000044209 Tumor Suppressor Genes Human genes 0.000 description 2
- 102100033649 Tumor necrosis factor alpha-induced protein 8 Human genes 0.000 description 2
- 102000007537 Type II DNA Topoisomerases Human genes 0.000 description 2
- 108010046308 Type II DNA Topoisomerases Proteins 0.000 description 2
- 102100022013 U1 small nuclear ribonucleoprotein A Human genes 0.000 description 2
- 101710177121 UDP-GalNAc:beta-1,3-N-acetylgalactosaminyltransferase 2 Proteins 0.000 description 2
- LFTYTUAZOPRMMI-NESSUJCYSA-N UDP-N-acetyl-alpha-D-galactosamine Chemical compound O1[C@H](CO)[C@H](O)[C@H](O)[C@@H](NC(=O)C)[C@H]1O[P@](O)(=O)O[P@](O)(=O)OC[C@@H]1[C@@H](O)[C@@H](O)[C@H](N2C(NC(=O)C=C2)=O)O1 LFTYTUAZOPRMMI-NESSUJCYSA-N 0.000 description 2
- LFTYTUAZOPRMMI-CFRASDGPSA-N UDP-N-acetyl-alpha-D-glucosamine Chemical compound O1[C@H](CO)[C@@H](O)[C@H](O)[C@@H](NC(=O)C)[C@H]1OP(O)(=O)OP(O)(=O)OC[C@@H]1[C@@H](O)[C@@H](O)[C@H](N2C(NC(=O)C=C2)=O)O1 LFTYTUAZOPRMMI-CFRASDGPSA-N 0.000 description 2
- IVOMOUWHDPKRLL-UHFFFAOYSA-N UNPD107823 Natural products O1C2COP(O)(=O)OC2C(O)C1N1C(N=CN=C2N)=C2N=C1 IVOMOUWHDPKRLL-UHFFFAOYSA-N 0.000 description 2
- 102100039931 Ubiquilin-like protein Human genes 0.000 description 2
- 101710188886 Ubiquitin-protein ligase E3A Proteins 0.000 description 2
- 102100026769 Unconventional myosin-XIX Human genes 0.000 description 2
- 101710193504 Unconventional myosin-XVIIIa Proteins 0.000 description 2
- DRTQHJPVMGBUCF-XVFCMESISA-N Uridine Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C=C1 DRTQHJPVMGBUCF-XVFCMESISA-N 0.000 description 2
- 208000006105 Uterine Cervical Neoplasms Diseases 0.000 description 2
- 206010046865 Vaccinia virus infection Diseases 0.000 description 2
- 102100035071 Vimentin Human genes 0.000 description 2
- 108010065472 Vimentin Proteins 0.000 description 2
- 108010066342 Virus Receptors Proteins 0.000 description 2
- 102000018265 Virus Receptors Human genes 0.000 description 2
- 241000700605 Viruses Species 0.000 description 2
- 102000003734 Voltage-Gated Potassium Channels Human genes 0.000 description 2
- 108090000013 Voltage-Gated Potassium Channels Proteins 0.000 description 2
- 102100025482 Voltage-dependent T-type calcium channel subunit alpha-1H Human genes 0.000 description 2
- 102100038143 WASH complex subunit 4 Human genes 0.000 description 2
- 102100038102 Whirlin Human genes 0.000 description 2
- 101710155241 Whirlin Proteins 0.000 description 2
- 241000269368 Xenopus laevis Species 0.000 description 2
- 101000744521 Xenopus laevis RNA-binding protein 24-A Proteins 0.000 description 2
- 102100034984 Zinc finger protein 770 Human genes 0.000 description 2
- 108010023249 Zyxin Proteins 0.000 description 2
- MXGLYEVGJRXBTP-QOLULZROSA-N [(6z,10e,14e)-3,7,11,15,19-pentamethylicosa-6,10,14,18-tetraenyl] phosphono hydrogen phosphate Chemical compound OP(=O)(O)OP(O)(=O)OCCC(C)CC\C=C(\C)CC\C=C(/C)CC\C=C(/C)CCC=C(C)C MXGLYEVGJRXBTP-QOLULZROSA-N 0.000 description 2
- JLCPHMBAVCMARE-UHFFFAOYSA-N [3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-hydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methyl [5-(6-aminopurin-9-yl)-2-(hydroxymethyl)oxolan-3-yl] hydrogen phosphate Polymers Cc1cn(C2CC(OP(O)(=O)OCC3OC(CC3OP(O)(=O)OCC3OC(CC3O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c3nc(N)[nH]c4=O)C(COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3CO)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cc(C)c(=O)[nH]c3=O)n3cc(C)c(=O)[nH]c3=O)n3ccc(N)nc3=O)n3cc(C)c(=O)[nH]c3=O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)O2)c(=O)[nH]c1=O JLCPHMBAVCMARE-UHFFFAOYSA-N 0.000 description 2
- 102100039167 [Pyruvate dehydrogenase [acetyl-transferring]]-phosphatase 2, mitochondrial Human genes 0.000 description 2
- 238000002835 absorbance Methods 0.000 description 2
- 108010087178 adiponutrin Proteins 0.000 description 2
- 238000001042 affinity chromatography Methods 0.000 description 2
- 235000004279 alanine Nutrition 0.000 description 2
- 230000000259 anti-tumor effect Effects 0.000 description 2
- 230000006907 apoptotic process Effects 0.000 description 2
- 239000007864 aqueous solution Substances 0.000 description 2
- MSWZFWKMSRAUBD-UHFFFAOYSA-N beta-D-galactosamine Natural products NC1C(O)OC(CO)C(O)C1O MSWZFWKMSRAUBD-UHFFFAOYSA-N 0.000 description 2
- WQZGKKKJIJFFOK-FPRJBGLDSA-N beta-D-galactose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@H]1O WQZGKKKJIJFFOK-FPRJBGLDSA-N 0.000 description 2
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 2
- 108010005774 beta-Galactosidase Proteins 0.000 description 2
- 210000004369 blood Anatomy 0.000 description 2
- 239000008280 blood Substances 0.000 description 2
- 210000000988 bone and bone Anatomy 0.000 description 2
- 210000001185 bone marrow Anatomy 0.000 description 2
- 210000000481 breast Anatomy 0.000 description 2
- 108010086826 calponin Proteins 0.000 description 2
- 102000006783 calponin Human genes 0.000 description 2
- 230000030833 cell death Effects 0.000 description 2
- 239000002771 cell marker Substances 0.000 description 2
- 230000001413 cellular effect Effects 0.000 description 2
- 238000005119 centrifugation Methods 0.000 description 2
- 201000010881 cervical cancer Diseases 0.000 description 2
- WNPXRNJEBMRJGV-UHFFFAOYSA-N chembl1399590 Chemical compound COC1=CC=CC(C=2N=C3C=CC=CC3=C(N3C(CCCC3)C)N=2)=C1O WNPXRNJEBMRJGV-UHFFFAOYSA-N 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 description 2
- 238000004587 chromatography analysis Methods 0.000 description 2
- 238000003776 cleavage reaction Methods 0.000 description 2
- 239000013599 cloning vector Substances 0.000 description 2
- 230000003081 coactivator Effects 0.000 description 2
- 238000001360 collision-induced dissociation Methods 0.000 description 2
- 229940095074 cyclic amp Drugs 0.000 description 2
- 230000006378 damage Effects 0.000 description 2
- 101150077768 ddb1 gene Proteins 0.000 description 2
- 239000005547 deoxyribonucleotide Substances 0.000 description 2
- 125000002637 deoxyribonucleotide group Chemical group 0.000 description 2
- 239000003599 detergent Substances 0.000 description 2
- 238000011161 development Methods 0.000 description 2
- 230000018109 developmental process Effects 0.000 description 2
- 108010057167 dimethylaniline monooxygenase (N-oxide forming) Proteins 0.000 description 2
- 210000003162 effector t lymphocyte Anatomy 0.000 description 2
- 210000002472 endoplasmic reticulum Anatomy 0.000 description 2
- 210000002889 endothelial cell Anatomy 0.000 description 2
- 230000009762 endothelial cell differentiation Effects 0.000 description 2
- 230000003511 endothelial effect Effects 0.000 description 2
- 239000002158 endotoxin Substances 0.000 description 2
- 230000002708 enhancing effect Effects 0.000 description 2
- 229940088598 enzyme Drugs 0.000 description 2
- 230000000925 erythroid effect Effects 0.000 description 2
- 210000003527 eukaryotic cell Anatomy 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 108700002148 exportin 1 Proteins 0.000 description 2
- 239000000284 extract Substances 0.000 description 2
- 230000006870 function Effects 0.000 description 2
- 239000005350 fused silica glass Substances 0.000 description 2
- 102000037865 fusion proteins Human genes 0.000 description 2
- 108020001507 fusion proteins Proteins 0.000 description 2
- 150000002270 gangliosides Chemical class 0.000 description 2
- 229960002442 glucosamine Drugs 0.000 description 2
- UYTPUPDQBNUYGX-UHFFFAOYSA-N guanine Chemical group O=C1NC(N)=NC2=C1N=CN2 UYTPUPDQBNUYGX-UHFFFAOYSA-N 0.000 description 2
- 230000036541 health Effects 0.000 description 2
- 231100000844 hepatocellular carcinoma Toxicity 0.000 description 2
- 238000012165 high-throughput sequencing Methods 0.000 description 2
- CUOPXNHMMIAXEF-AKRYILKSSA-N histatin 1 Chemical compound C([C@@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(N)=O)C(O)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CO)NC(=O)CNC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CC(O)=O)NC(=O)CNC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CC=1NC=NC=1)NC(=O)[C@H](CO)NC(=O)[C@H](CC=1NC=NC=1)NC(=O)[C@H](CC=1NC=NC=1)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CC=1NC=NC=1)NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)CNC(=O)[C@H](CC=1NC=NC=1)NC(=O)[C@H](CC=1NC=NC=1)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CC=1NC=NC=1)NC(=O)[C@H](COP(O)(O)=O)NC(=O)[C@@H](N)CC(O)=O)C1=CC=C(O)C=C1 CUOPXNHMMIAXEF-AKRYILKSSA-N 0.000 description 2
- 102000027596 immune receptors Human genes 0.000 description 2
- 108091008915 immune receptors Proteins 0.000 description 2
- 230000005847 immunogenicity Effects 0.000 description 2
- 102000018358 immunoglobulin Human genes 0.000 description 2
- 238000011534 incubation Methods 0.000 description 2
- 230000003993 interaction Effects 0.000 description 2
- 238000002955 isolation Methods 0.000 description 2
- 108010045069 keyhole-limpet hemocyanin Proteins 0.000 description 2
- 210000002415 kinetochore Anatomy 0.000 description 2
- 238000002372 labelling Methods 0.000 description 2
- FCCDDURTIIUXBY-UHFFFAOYSA-N lipoamide Chemical compound NC(=O)CCCCC1CCSS1 FCCDDURTIIUXBY-UHFFFAOYSA-N 0.000 description 2
- 229920006008 lipopolysaccharide Polymers 0.000 description 2
- 108010053687 macrogolgin Proteins 0.000 description 2
- 238000012423 maintenance Methods 0.000 description 2
- 230000036210 malignancy Effects 0.000 description 2
- 210000004962 mammalian cell Anatomy 0.000 description 2
- 238000004949 mass spectrometry Methods 0.000 description 2
- 238000012737 microarray-based gene expression Methods 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 238000012243 multiplex automated genomic engineering Methods 0.000 description 2
- JEUXZUSUYIHGNL-UHFFFAOYSA-N n,n-diethylethanamine;hydrate Chemical compound O.CCN(CC)CC JEUXZUSUYIHGNL-UHFFFAOYSA-N 0.000 description 2
- 108010042350 neurotrimin Proteins 0.000 description 2
- 231100000252 nontoxic Toxicity 0.000 description 2
- 230000003000 nontoxic effect Effects 0.000 description 2
- 208000027014 optic atrophy 1 Diseases 0.000 description 2
- 210000003254 palate Anatomy 0.000 description 2
- 230000000858 peroxisomal effect Effects 0.000 description 2
- 239000008194 pharmaceutical composition Substances 0.000 description 2
- 239000000546 pharmaceutical excipient Substances 0.000 description 2
- YBYRMVIVWMBXKQ-UHFFFAOYSA-N phenylmethanesulfonyl fluoride Chemical compound FS(=O)(=O)CC1=CC=CC=C1 YBYRMVIVWMBXKQ-UHFFFAOYSA-N 0.000 description 2
- 108010043629 phosphatidylinositol-3,4-bisphosphate 4-phosphatase Proteins 0.000 description 2
- 102000002022 plexin Human genes 0.000 description 2
- 108050009312 plexin Proteins 0.000 description 2
- 230000029279 positive regulation of transcription, DNA-dependent Effects 0.000 description 2
- 239000011591 potassium Substances 0.000 description 2
- 229910052700 potassium Inorganic materials 0.000 description 2
- 230000002062 proliferating effect Effects 0.000 description 2
- 108010042589 prolyl T RNA synthetase Proteins 0.000 description 2
- 239000003380 propellant Substances 0.000 description 2
- 230000000069 prophylactic effect Effects 0.000 description 2
- 238000011321 prophylaxis Methods 0.000 description 2
- 108020003519 protein disulfide isomerase Proteins 0.000 description 2
- 230000025220 protein targeting to vacuole Effects 0.000 description 2
- 238000007347 radical substitution reaction Methods 0.000 description 2
- 230000009257 reactivity Effects 0.000 description 2
- 230000007115 recruitment Effects 0.000 description 2
- 230000022983 regulation of cell cycle Effects 0.000 description 2
- 230000010076 replication Effects 0.000 description 2
- 230000001850 reproductive effect Effects 0.000 description 2
- 230000022120 response to tumor cell Effects 0.000 description 2
- 230000007017 scission Effects 0.000 description 2
- 230000003248 secreting effect Effects 0.000 description 2
- 238000012163 sequencing technique Methods 0.000 description 2
- 210000002966 serum Anatomy 0.000 description 2
- 239000011734 sodium Substances 0.000 description 2
- 229910052708 sodium Inorganic materials 0.000 description 2
- 239000008247 solid mixture Substances 0.000 description 2
- 230000007046 spindle assembly involved in mitosis Effects 0.000 description 2
- 210000000130 stem cell Anatomy 0.000 description 2
- 230000001629 suppression Effects 0.000 description 2
- 238000004885 tandem mass spectrometry Methods 0.000 description 2
- 230000002103 transcriptional effect Effects 0.000 description 2
- 238000001890 transfection Methods 0.000 description 2
- 238000012546 transfer Methods 0.000 description 2
- 230000001131 transforming effect Effects 0.000 description 2
- 108010031667 trichohyalin Proteins 0.000 description 2
- AVBGNFCMKJOFIN-UHFFFAOYSA-N triethylammonium acetate Chemical compound CC(O)=O.CCN(CC)CC AVBGNFCMKJOFIN-UHFFFAOYSA-N 0.000 description 2
- 239000012588 trypsin Substances 0.000 description 2
- 241000701161 unidentified adenovirus Species 0.000 description 2
- 208000007089 vaccinia Diseases 0.000 description 2
- 210000005048 vimentin Anatomy 0.000 description 2
- 230000003612 virological effect Effects 0.000 description 2
- UHDGCWIWMRVCDJ-UHFFFAOYSA-N 1-beta-D-Xylofuranosyl-NH-Cytosine Natural products O=C1N=C(N)C=CN1C1C(O)C(O)C(CO)O1 UHDGCWIWMRVCDJ-UHFFFAOYSA-N 0.000 description 1
- IIZPXYDJLKNOIY-JXPKJXOSSA-N 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCC\C=C/C\C=C/C\C=C/C\C=C/CCCCC IIZPXYDJLKNOIY-JXPKJXOSSA-N 0.000 description 1
- MCKAJXMRULSUKI-CNWJWELYSA-N 1D-myo-inositol 3,4-bisphosphate Chemical compound O[C@H]1[C@H](O)[C@@H](O)[C@H](OP(O)(O)=O)[C@@H](OP(O)(O)=O)[C@H]1O MCKAJXMRULSUKI-CNWJWELYSA-N 0.000 description 1
- UMCMPZBLKLEWAF-BCTGSCMUSA-N 3-[(3-cholamidopropyl)dimethylammonio]propane-1-sulfonate Chemical compound C([C@H]1C[C@H]2O)[C@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H]([C@@H](CCC(=O)NCCC[N+](C)(C)CCCS([O-])(=O)=O)C)[C@@]2(C)[C@@H](O)C1 UMCMPZBLKLEWAF-BCTGSCMUSA-N 0.000 description 1
- FWMNVWWHGCHHJJ-SKKKGAJSSA-N 4-amino-1-[(2r)-6-amino-2-[[(2r)-2-[[(2r)-2-[[(2r)-2-amino-3-phenylpropanoyl]amino]-3-phenylpropanoyl]amino]-4-methylpentanoyl]amino]hexanoyl]piperidine-4-carboxylic acid Chemical compound C([C@H](C(=O)N[C@H](CC(C)C)C(=O)N[C@H](CCCCN)C(=O)N1CCC(N)(CC1)C(O)=O)NC(=O)[C@H](N)CC=1C=CC=CC=1)C1=CC=CC=C1 FWMNVWWHGCHHJJ-SKKKGAJSSA-N 0.000 description 1
- JYCQQPHGFMYQCF-UHFFFAOYSA-N 4-tert-Octylphenol monoethoxylate Chemical compound CC(C)(C)CC(C)(C)C1=CC=C(OCCO)C=C1 JYCQQPHGFMYQCF-UHFFFAOYSA-N 0.000 description 1
- 102100037563 40S ribosomal protein S2 Human genes 0.000 description 1
- 101710107640 40S ribosomal protein S2 Proteins 0.000 description 1
- 101710107639 40S ribosomal protein S4 Proteins 0.000 description 1
- 102100024088 40S ribosomal protein S7 Human genes 0.000 description 1
- 101710107649 40S ribosomal protein S7 Proteins 0.000 description 1
- 102100021206 60S ribosomal protein L19 Human genes 0.000 description 1
- 101710187808 60S ribosomal protein L19 Proteins 0.000 description 1
- 102100036116 60S ribosomal protein L35 Human genes 0.000 description 1
- 108700037626 60S ribosomal protein L35 Proteins 0.000 description 1
- 102100035841 60S ribosomal protein L7 Human genes 0.000 description 1
- 101710117443 60S ribosomal protein L7 Proteins 0.000 description 1
- 108010011122 A Kinase Anchor Proteins Proteins 0.000 description 1
- 101710120455 A-kinase anchor protein 10, mitochondrial Proteins 0.000 description 1
- 108050003506 ABL interactor 2 Proteins 0.000 description 1
- 108091007505 ADAM17 Proteins 0.000 description 1
- 102100027783 ADP-ribose glycohydrolase OARD1 Human genes 0.000 description 1
- 101710081984 AT-rich interactive domain-containing protein 4A Proteins 0.000 description 1
- 101710162331 ATP synthase-coupling factor 6, mitochondrial Proteins 0.000 description 1
- 102000005416 ATP-Binding Cassette Transporters Human genes 0.000 description 1
- 108010006533 ATP-Binding Cassette Transporters Proteins 0.000 description 1
- 102100037128 ATP-binding cassette sub-family C member 10 Human genes 0.000 description 1
- 101710093330 ATP-binding cassette sub-family C member 10 Proteins 0.000 description 1
- 102100037129 ATP-binding cassette sub-family C member 11 Human genes 0.000 description 1
- 102100028221 Abl interactor 2 Human genes 0.000 description 1
- 101000983256 Acanthamoeba polyphaga mimivirus Putative prolyl 4-hydroxylase Proteins 0.000 description 1
- RZVAJINKPMORJF-UHFFFAOYSA-N Acetaminophen Chemical compound CC(=O)NC1=CC=C(O)C=C1 RZVAJINKPMORJF-UHFFFAOYSA-N 0.000 description 1
- 102100029374 Adapter molecule crk Human genes 0.000 description 1
- 101710092082 Adapter molecule crk Proteins 0.000 description 1
- 108700028369 Alleles Proteins 0.000 description 1
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
- 102100031090 Alpha-catulin Human genes 0.000 description 1
- 101710170885 Alpha-catulin Proteins 0.000 description 1
- 108010031677 Anaphase-Promoting Complex-Cyclosome Proteins 0.000 description 1
- 102000005446 Anaphase-Promoting Complex-Cyclosome Human genes 0.000 description 1
- 102100033695 Anaphase-promoting complex subunit 13 Human genes 0.000 description 1
- 101710155999 Anaphase-promoting complex subunit 13 Proteins 0.000 description 1
- 102100033901 Ankyrin repeat and SOCS box protein 17 Human genes 0.000 description 1
- 101710181640 Ankyrin repeat and SOCS box protein 17 Proteins 0.000 description 1
- 108010049777 Ankyrins Proteins 0.000 description 1
- 102000008102 Ankyrins Human genes 0.000 description 1
- 102100036523 Anoctamin-6 Human genes 0.000 description 1
- 108050008800 Anoctamin-6 Proteins 0.000 description 1
- 101710145634 Antigen 1 Proteins 0.000 description 1
- 102100021987 Apoptosis-stimulating of p53 protein 1 Human genes 0.000 description 1
- 101710091628 Apoptosis-stimulating of p53 protein 1 Proteins 0.000 description 1
- 102100033367 Appetite-regulating hormone Human genes 0.000 description 1
- 101710111255 Appetite-regulating hormone Proteins 0.000 description 1
- 101000823234 Arabidopsis thaliana ABC transporter C family member 6 Proteins 0.000 description 1
- 101000843118 Arabidopsis thaliana Very-long-chain (3R)-3-hydroxyacyl-CoA dehydratase PASTICCINO 2 Proteins 0.000 description 1
- 108010004586 Ataxia Telangiectasia Mutated Proteins Proteins 0.000 description 1
- 108091008875 B cell receptors Proteins 0.000 description 1
- 101710113110 B-cell receptor-associated protein 31 Proteins 0.000 description 1
- 101710168437 BCL-6 corepressor Proteins 0.000 description 1
- 101150072950 BRCA1 gene Proteins 0.000 description 1
- 102000008836 BTB/POZ domains Human genes 0.000 description 1
- 108050000749 BTB/POZ domains Proteins 0.000 description 1
- 241000894006 Bacteria Species 0.000 description 1
- 102100033943 Basic salivary proline-rich protein 2 Human genes 0.000 description 1
- 102100024475 Beta-defensin 119 Human genes 0.000 description 1
- 101710187210 Beta-defensin 119 Proteins 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical compound OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 1
- 108010040422 Bone Morphogenetic Protein Receptors Proteins 0.000 description 1
- 102000001893 Bone Morphogenetic Protein Receptors Human genes 0.000 description 1
- 102100025422 Bone morphogenetic protein receptor type-2 Human genes 0.000 description 1
- 108050008407 Bone morphogenetic protein receptor type-2 Proteins 0.000 description 1
- 241000283690 Bos taurus Species 0.000 description 1
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 1
- 102100025399 Breast cancer type 2 susceptibility protein Human genes 0.000 description 1
- 101710089613 Breast cancer type 2 susceptibility protein Proteins 0.000 description 1
- 108010014064 CCCTC-Binding Factor Proteins 0.000 description 1
- 108010029697 CD40 Ligand Proteins 0.000 description 1
- 102100032937 CD40 ligand Human genes 0.000 description 1
- 101800000267 CD40 ligand, soluble form Proteins 0.000 description 1
- 102400000432 CD40 ligand, soluble form Human genes 0.000 description 1
- 102100035793 CD83 antigen Human genes 0.000 description 1
- 101100381481 Caenorhabditis elegans baz-2 gene Proteins 0.000 description 1
- 102100039319 Calcium release-activated calcium channel protein 1 Human genes 0.000 description 1
- 108050007758 Caldesmon Proteins 0.000 description 1
- 241000283707 Capra Species 0.000 description 1
- 101710106619 Catenin alpha-3 Proteins 0.000 description 1
- 102100032230 Caveolae-associated protein 1 Human genes 0.000 description 1
- 102000011068 Cdc42 Human genes 0.000 description 1
- 108050001278 Cdc42 Proteins 0.000 description 1
- 101710083565 Cell cycle checkpoint protein RAD17 Proteins 0.000 description 1
- 102100025051 Cell division control protein 42 homolog Human genes 0.000 description 1
- 102100036569 Cell division cycle and apoptosis regulator protein 1 Human genes 0.000 description 1
- 101710189019 Cell division cycle and apoptosis regulator protein 1 Proteins 0.000 description 1
- 102100025064 Cellular tumor antigen p53 Human genes 0.000 description 1
- 102100025829 Centrosomal protein of 97 kDa Human genes 0.000 description 1
- 241000282693 Cercopithecidae Species 0.000 description 1
- 102000034573 Channels Human genes 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- 101710100756 Choline-phosphate cytidylyltransferase B Proteins 0.000 description 1
- 102100020736 Chromosome-associated kinesin KIF4A Human genes 0.000 description 1
- 108090000317 Chymotrypsin Proteins 0.000 description 1
- 102100033361 Cilium assembly protein DZIP1 Human genes 0.000 description 1
- 101710204168 Coagulation factor VIII Proteins 0.000 description 1
- 108020004705 Codon Proteins 0.000 description 1
- 102100031087 Coiled-coil domain-containing protein 18 Human genes 0.000 description 1
- 102100023755 Coiled-coil domain-containing protein 192 Human genes 0.000 description 1
- 102100023714 Coiled-coil domain-containing protein 73 Human genes 0.000 description 1
- 208000035473 Communicable disease Diseases 0.000 description 1
- 108010047041 Complementarity Determining Regions Proteins 0.000 description 1
- 108010002947 Connectin Proteins 0.000 description 1
- 102000005636 Cyclic AMP Response Element-Binding Protein Human genes 0.000 description 1
- 108010045171 Cyclic AMP Response Element-Binding Protein Proteins 0.000 description 1
- 108090000264 Cyclin I Proteins 0.000 description 1
- 102000003907 Cyclin I Human genes 0.000 description 1
- 108010072220 Cyclophilin A Proteins 0.000 description 1
- UHDGCWIWMRVCDJ-PSQAKQOGSA-N Cytidine Natural products O=C1N=C(N)C=CN1[C@@H]1[C@@H](O)[C@@H](O)[C@H](CO)O1 UHDGCWIWMRVCDJ-PSQAKQOGSA-N 0.000 description 1
- 108010009911 Cytochrome P-450 CYP11B2 Proteins 0.000 description 1
- 102100024329 Cytochrome P450 11B2, mitochondrial Human genes 0.000 description 1
- 101710170719 Cytochrome P450 11B2, mitochondrial Proteins 0.000 description 1
- 102100029080 Cytochrome c oxidase assembly protein COX14 Human genes 0.000 description 1
- 101710173353 Cytotoxicity-associated immunodominant antigen Proteins 0.000 description 1
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 1
- 150000008574 D-amino acids Chemical class 0.000 description 1
- 102000004594 DNA Polymerase I Human genes 0.000 description 1
- 108010017826 DNA Polymerase I Proteins 0.000 description 1
- 108090000323 DNA Topoisomerases Proteins 0.000 description 1
- 102000003915 DNA Topoisomerases Human genes 0.000 description 1
- 102100022307 DNA polymerase alpha catalytic subunit Human genes 0.000 description 1
- 101710174969 DNA polymerase alpha catalytic subunit Proteins 0.000 description 1
- 230000006820 DNA synthesis Effects 0.000 description 1
- 102100031230 DNA topoisomerase I, mitochondrial Human genes 0.000 description 1
- 101710094860 DNA topoisomerase I, mitochondrial Proteins 0.000 description 1
- 241000450599 DNA viruses Species 0.000 description 1
- 102000000371 Dedicator of cytokinesis Human genes 0.000 description 1
- 108050008931 Dedicator of cytokinesis Proteins 0.000 description 1
- 102100031601 Dedicator of cytokinesis protein 11 Human genes 0.000 description 1
- 101000697358 Dictyostelium discoideum FACT complex subunit SSRP1 Proteins 0.000 description 1
- 102100035041 Dimethylaniline monooxygenase [N-oxide-forming] 3 Human genes 0.000 description 1
- 206010061818 Disease progression Diseases 0.000 description 1
- 102100035420 DnaJ homolog subfamily C member 1 Human genes 0.000 description 1
- 101710138829 DnaJ homolog subfamily C member 1 Proteins 0.000 description 1
- 241000255581 Drosophila <fruit fly, genus> Species 0.000 description 1
- 101000926719 Drosophila melanogaster Cilium assembly protein DZIP1L Proteins 0.000 description 1
- 101001099988 Drosophila melanogaster DNA repair protein Rad51 homolog Proteins 0.000 description 1
- 101100482131 Drosophila melanogaster Trf4-2 gene Proteins 0.000 description 1
- 101100373143 Drosophila melanogaster Wnt5 gene Proteins 0.000 description 1
- 102000013798 Dynamin-like 120kDa protein, mitochondrial Human genes 0.000 description 1
- 108050003616 Dynamin-like 120kDa protein, mitochondrial Proteins 0.000 description 1
- 102100023149 E3 ubiquitin-protein ligase MARCHF6 Human genes 0.000 description 1
- 102100037359 EF-hand calcium-binding domain-containing protein 13 Human genes 0.000 description 1
- 102100031947 EGF domain-specific O-linked N-acetylglucosamine transferase Human genes 0.000 description 1
- 102000004533 Endonucleases Human genes 0.000 description 1
- 108010042407 Endonucleases Proteins 0.000 description 1
- 102000005593 Endopeptidases Human genes 0.000 description 1
- 108010059378 Endopeptidases Proteins 0.000 description 1
- 102100023387 Endoribonuclease Dicer Human genes 0.000 description 1
- 102100039369 Epidermal growth factor receptor substrate 15 Human genes 0.000 description 1
- 101710091542 Epidermal growth factor receptor substrate 15 Proteins 0.000 description 1
- 102100036725 Epithelial discoidin domain-containing receptor 1 Human genes 0.000 description 1
- 102100036816 Eukaryotic peptide chain release factor GTP-binding subunit ERF3A Human genes 0.000 description 1
- 101710151739 Eukaryotic peptide chain release factor GTP-binding subunit ERF3A Proteins 0.000 description 1
- 101710109043 Eukaryotic translation initiation factor 3 subunit A Proteins 0.000 description 1
- 101710109047 Eukaryotic translation initiation factor 3 subunit B Proteins 0.000 description 1
- 102000010834 Extracellular Matrix Proteins Human genes 0.000 description 1
- 108010037362 Extracellular Matrix Proteins Proteins 0.000 description 1
- 102100037122 Extracellular matrix organizing protein FRAS1 Human genes 0.000 description 1
- 108010043287 F(6) ATPase Proteins 0.000 description 1
- 102100038578 F-box only protein 11 Human genes 0.000 description 1
- 102100037316 F-box/LRR-repeat protein 4 Human genes 0.000 description 1
- 102100025637 FACT complex subunit SPT16 Human genes 0.000 description 1
- 101710104971 FACT complex subunit SPT16 Proteins 0.000 description 1
- 102100035441 FRAS1-related extracellular matrix protein 2 Human genes 0.000 description 1
- 101710168206 FRAS1-related extracellular matrix protein 2 Proteins 0.000 description 1
- 102100035261 FYN-binding protein 1 Human genes 0.000 description 1
- 102000015212 Fas Ligand Protein Human genes 0.000 description 1
- 108010087819 Fc receptors Proteins 0.000 description 1
- 102000009109 Fc receptors Human genes 0.000 description 1
- 102100032596 Fibrocystin Human genes 0.000 description 1
- 101710182545 Fibrocystin Proteins 0.000 description 1
- 102100031812 Fibulin-1 Human genes 0.000 description 1
- 101710170731 Fibulin-1 Proteins 0.000 description 1
- 108010029961 Filgrastim Proteins 0.000 description 1
- MNFMIVVPXOGUMX-UHFFFAOYSA-N Fluchloralin Chemical compound CCCN(CCCl)C1=C([N+]([O-])=O)C=C(C(F)(F)F)C=C1[N+]([O-])=O MNFMIVVPXOGUMX-UHFFFAOYSA-N 0.000 description 1
- 208000000666 Fowlpox Diseases 0.000 description 1
- 102100030279 G-protein coupled receptor 35 Human genes 0.000 description 1
- 102100033061 G-protein coupled receptor 55 Human genes 0.000 description 1
- 108091006094 GTPase-accelerating proteins Proteins 0.000 description 1
- 102100034327 Ganglioside-induced differentiation-associated protein 1-like 1 Human genes 0.000 description 1
- 101710100980 Ganglioside-induced differentiation-associated protein 1-like 1 Proteins 0.000 description 1
- 108700007698 Genetic Terminator Regions Proteins 0.000 description 1
- 108010016122 Ghrelin Receptors Proteins 0.000 description 1
- 102000005720 Glutathione transferase Human genes 0.000 description 1
- 108010070675 Glutathione transferase Proteins 0.000 description 1
- 239000004471 Glycine Substances 0.000 description 1
- 108010017080 Granulocyte Colony-Stimulating Factor Proteins 0.000 description 1
- 102000009465 Growth Factor Receptors Human genes 0.000 description 1
- 108010009202 Growth Factor Receptors Proteins 0.000 description 1
- 108010067218 Guanine Nucleotide Exchange Factors Proteins 0.000 description 1
- 102000016285 Guanine Nucleotide Exchange Factors Human genes 0.000 description 1
- 108010091938 HLA-B7 Antigen Proteins 0.000 description 1
- 108010039075 HLA-B8 Antigen Proteins 0.000 description 1
- 108010042283 HSP40 Heat-Shock Proteins Proteins 0.000 description 1
- 102000004447 HSP40 Heat-Shock Proteins Human genes 0.000 description 1
- 102100031573 Hematopoietic progenitor cell antigen CD34 Human genes 0.000 description 1
- 208000005331 Hepatitis D Diseases 0.000 description 1
- 208000037262 Hepatitis delta Diseases 0.000 description 1
- 101710130089 Heterogeneous nuclear ribonucleoprotein C-like 1 Proteins 0.000 description 1
- 108010019372 Heterogeneous-Nuclear Ribonucleoproteins Proteins 0.000 description 1
- 102000006479 Heterogeneous-Nuclear Ribonucleoproteins Human genes 0.000 description 1
- 241000238631 Hexapoda Species 0.000 description 1
- 102100022103 Histone-lysine N-methyltransferase 2A Human genes 0.000 description 1
- 108050002855 Histone-lysine N-methyltransferase 2A Proteins 0.000 description 1
- 108010033040 Histones Proteins 0.000 description 1
- 102100032827 Homeodomain-interacting protein kinase 2 Human genes 0.000 description 1
- 101710110793 Homeodomain-interacting protein kinase 2 Proteins 0.000 description 1
- 101001008861 Homo sapiens ADP-ribose glycohydrolase OARD1 Proteins 0.000 description 1
- 101001029057 Homo sapiens ATP-binding cassette sub-family C member 11 Proteins 0.000 description 1
- 101001068639 Homo sapiens Basic salivary proline-rich protein 2 Proteins 0.000 description 1
- 101000946856 Homo sapiens CD83 antigen Proteins 0.000 description 1
- 101000777239 Homo sapiens Calcineurin B homologous protein 2 Proteins 0.000 description 1
- 101000745520 Homo sapiens Calcium release-activated calcium channel protein 1 Proteins 0.000 description 1
- 101000793727 Homo sapiens Caprin-1 Proteins 0.000 description 1
- 101000869049 Homo sapiens Caveolae-associated protein 1 Proteins 0.000 description 1
- 101000721661 Homo sapiens Cellular tumor antigen p53 Proteins 0.000 description 1
- 101000914244 Homo sapiens Centrosomal protein of 97 kDa Proteins 0.000 description 1
- 101001139157 Homo sapiens Chromosome-associated kinesin KIF4A Proteins 0.000 description 1
- 101000926718 Homo sapiens Cilium assembly protein DZIP1 Proteins 0.000 description 1
- 101000777411 Homo sapiens Coiled-coil domain-containing protein 18 Proteins 0.000 description 1
- 101000978235 Homo sapiens Coiled-coil domain-containing protein 192 Proteins 0.000 description 1
- 101000978316 Homo sapiens Coiled-coil domain-containing protein 73 Proteins 0.000 description 1
- 101000770621 Homo sapiens Cytochrome c oxidase assembly protein COX14 Proteins 0.000 description 1
- 101000866270 Homo sapiens Dedicator of cytokinesis protein 11 Proteins 0.000 description 1
- 101000978676 Homo sapiens E3 ubiquitin-protein ligase MARCHF6 Proteins 0.000 description 1
- 101000880228 Homo sapiens EF-hand calcium-binding domain-containing protein 13 Proteins 0.000 description 1
- 101000920640 Homo sapiens EGF domain-specific O-linked N-acetylglucosamine transferase Proteins 0.000 description 1
- 101000929433 Homo sapiens Epithelial discoidin domain-containing receptor 1 Proteins 0.000 description 1
- 101001029168 Homo sapiens Extracellular matrix organizing protein FRAS1 Proteins 0.000 description 1
- 101001030683 Homo sapiens F-box only protein 11 Proteins 0.000 description 1
- 101000697353 Homo sapiens FACT complex subunit SSRP1 Proteins 0.000 description 1
- 101001022163 Homo sapiens FYN-binding protein 1 Proteins 0.000 description 1
- 101000823456 Homo sapiens Fructose-2,6-bisphosphatase Proteins 0.000 description 1
- 101000746367 Homo sapiens Granulocyte colony-stimulating factor Proteins 0.000 description 1
- 101000763352 Homo sapiens Heat shock protein 75 kDa, mitochondrial Proteins 0.000 description 1
- 101000777663 Homo sapiens Hematopoietic progenitor cell antigen CD34 Proteins 0.000 description 1
- 101000852599 Homo sapiens Importin-13 Proteins 0.000 description 1
- 101000852852 Homo sapiens Innate immunity activator protein Proteins 0.000 description 1
- 101001011755 Homo sapiens Integrator complex subunit 7 Proteins 0.000 description 1
- 101001002709 Homo sapiens Interleukin-4 Proteins 0.000 description 1
- 101001043807 Homo sapiens Interleukin-7 Proteins 0.000 description 1
- 101000997838 Homo sapiens Janus kinase and microtubule-interacting protein 2 Proteins 0.000 description 1
- 101000579912 Homo sapiens Leucine-rich repeat-containing protein 58 Proteins 0.000 description 1
- 101000619643 Homo sapiens Ligand-dependent nuclear receptor-interacting factor 1 Proteins 0.000 description 1
- 101000917858 Homo sapiens Low affinity immunoglobulin gamma Fc region receptor III-A Proteins 0.000 description 1
- 101001137987 Homo sapiens Lymphocyte activation gene 3 protein Proteins 0.000 description 1
- 101000634835 Homo sapiens M1-specific T cell receptor alpha chain Proteins 0.000 description 1
- 101000946889 Homo sapiens Monocyte differentiation antigen CD14 Proteins 0.000 description 1
- 101000589010 Homo sapiens Myomesin-1 Proteins 0.000 description 1
- 101001041015 Homo sapiens Netrin receptor DCC Proteins 0.000 description 1
- 101000578295 Homo sapiens NmrA-like family domain-containing protein 1 Proteins 0.000 description 1
- 101000839399 Homo sapiens Oxidoreductase HTATIP2 Proteins 0.000 description 1
- 101001072715 Homo sapiens PiggyBac transposable element-derived protein 3 Proteins 0.000 description 1
- 101001001561 Homo sapiens Piwi-like protein 3 Proteins 0.000 description 1
- 101001113490 Homo sapiens Poly(A)-specific ribonuclease PARN Proteins 0.000 description 1
- 101001087352 Homo sapiens Poly(U)-binding-splicing factor PUF60 Proteins 0.000 description 1
- 101001026195 Homo sapiens Potassium voltage-gated channel subfamily A member 7 Proteins 0.000 description 1
- 101000870728 Homo sapiens Probable ATP-dependent RNA helicase DDX27 Proteins 0.000 description 1
- 101001033177 Homo sapiens Probable methyltransferase-like protein 23 Proteins 0.000 description 1
- 101000892360 Homo sapiens Protein AF-17 Proteins 0.000 description 1
- 101001116549 Homo sapiens Protein CBFA2T2 Proteins 0.000 description 1
- 101000625251 Homo sapiens Protein Mis18-alpha Proteins 0.000 description 1
- 101000657326 Homo sapiens Protein TANC2 Proteins 0.000 description 1
- 101000994790 Homo sapiens Ras GTPase-activating-like protein IQGAP2 Proteins 0.000 description 1
- 101000677110 Homo sapiens Ras-like protein family member 11A Proteins 0.000 description 1
- 101001012157 Homo sapiens Receptor tyrosine-protein kinase erbB-2 Proteins 0.000 description 1
- 101000703268 Homo sapiens Regulator of G-protein signaling protein-like Proteins 0.000 description 1
- 101000650588 Homo sapiens Roundabout homolog 3 Proteins 0.000 description 1
- 101000637705 Homo sapiens Ryanodine receptor 2 Proteins 0.000 description 1
- 101000881168 Homo sapiens SPARC Proteins 0.000 description 1
- 101000825571 Homo sapiens SUMO-interacting motif-containing protein 1 Proteins 0.000 description 1
- 101000864751 Homo sapiens Seizure protein 6 homolog Proteins 0.000 description 1
- 101000654668 Homo sapiens Septin-2 Proteins 0.000 description 1
- 101000709238 Homo sapiens Serine/threonine-protein kinase SIK1 Proteins 0.000 description 1
- 101000652369 Homo sapiens Spermatogenesis-associated protein 7 Proteins 0.000 description 1
- 101000634836 Homo sapiens T cell receptor alpha chain MC.7.G5 Proteins 0.000 description 1
- 101100462828 Homo sapiens TENT4B gene Proteins 0.000 description 1
- 101001063514 Homo sapiens Telomerase-binding protein EST1A Proteins 0.000 description 1
- 101000796022 Homo sapiens Thioredoxin-interacting protein Proteins 0.000 description 1
- 101000824979 Homo sapiens Transcription factor Sp4 Proteins 0.000 description 1
- 101000894428 Homo sapiens Transcriptional repressor CTCFL Proteins 0.000 description 1
- 101000633097 Homo sapiens Transient receptor potential cation channel subfamily V member 4 Proteins 0.000 description 1
- 101000638096 Homo sapiens Transmembrane channel-like protein 4 Proteins 0.000 description 1
- 101000653545 Homo sapiens Trichohyalin-like protein 1 Proteins 0.000 description 1
- 101000611183 Homo sapiens Tumor necrosis factor Proteins 0.000 description 1
- 101000671653 Homo sapiens U3 small nucleolar RNA-associated protein 14 homolog A Proteins 0.000 description 1
- 101000805909 Homo sapiens U3 small nucleolar RNA-associated protein 6 homolog Proteins 0.000 description 1
- 101000884255 Homo sapiens Uncharacterized protein C4orf36 Proteins 0.000 description 1
- 101001030255 Homo sapiens Unconventional myosin-XVIIIa Proteins 0.000 description 1
- 101000851018 Homo sapiens Vascular endothelial growth factor receptor 1 Proteins 0.000 description 1
- 101000964427 Homo sapiens Zinc finger and BTB domain-containing protein 14 Proteins 0.000 description 1
- 101000782222 Homo sapiens von Willebrand factor C and EGF domain-containing protein Proteins 0.000 description 1
- 241000725303 Human immunodeficiency virus Species 0.000 description 1
- 101710172715 Hydrolase 3 Proteins 0.000 description 1
- 102000001284 I-kappa-B kinase Human genes 0.000 description 1
- 108060006678 I-kappa-B kinase Proteins 0.000 description 1
- 108091008585 IP3 receptors Proteins 0.000 description 1
- 102100036724 Innate immunity activator protein Human genes 0.000 description 1
- 102000007640 Inositol 1,4,5-Trisphosphate Receptors Human genes 0.000 description 1
- 108010048077 Inositol 1,4,5-trisphosphate 3-kinase Proteins 0.000 description 1
- 108090000723 Insulin-Like Growth Factor I Proteins 0.000 description 1
- 102000014429 Insulin-like growth factor Human genes 0.000 description 1
- 102100030147 Integrator complex subunit 7 Human genes 0.000 description 1
- 101800000875 Integrin alpha-3 heavy chain Proteins 0.000 description 1
- 101800001159 Integrin alpha-3 light chain Proteins 0.000 description 1
- 102000017316 Integrin beta-8 subunit Human genes 0.000 description 1
- 102000014746 Interferon-Stimulated Gene Factor 3 Human genes 0.000 description 1
- 108010064052 Interferon-Stimulated Gene Factor 3 Proteins 0.000 description 1
- 102000008070 Interferon-gamma Human genes 0.000 description 1
- 102000000588 Interleukin-2 Human genes 0.000 description 1
- 108010002386 Interleukin-3 Proteins 0.000 description 1
- 102000000646 Interleukin-3 Human genes 0.000 description 1
- 102000004388 Interleukin-4 Human genes 0.000 description 1
- 108090000978 Interleukin-4 Proteins 0.000 description 1
- 108091092195 Intron Proteins 0.000 description 1
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 1
- 108010044467 Isoenzymes Proteins 0.000 description 1
- 102100033439 Janus kinase and microtubule-interacting protein 2 Human genes 0.000 description 1
- 102100027615 Kelch-like protein 8 Human genes 0.000 description 1
- 108050002494 Kelch-like protein 8 Proteins 0.000 description 1
- 102000010638 Kinesin Human genes 0.000 description 1
- 108010063296 Kinesin Proteins 0.000 description 1
- 102100027927 Kinesin-like protein KIF6 Human genes 0.000 description 1
- 101710152742 Kinesin-like protein KIF6 Proteins 0.000 description 1
- 108010012048 Kisspeptins Proteins 0.000 description 1
- 102000013599 Kisspeptins Human genes 0.000 description 1
- 102000016996 Kisspeptins receptors Human genes 0.000 description 1
- 108070000011 Kisspeptins receptors Proteins 0.000 description 1
- 102100020880 Kit ligand Human genes 0.000 description 1
- 101710177504 Kit ligand Proteins 0.000 description 1
- 125000000998 L-alanino group Chemical group [H]N([*])[C@](C([H])([H])[H])([H])C(=O)O[H] 0.000 description 1
- DCXYFEDJOCDNAF-REOHCLBHSA-N L-asparagine Chemical compound OC(=O)[C@@H](N)CC(N)=O DCXYFEDJOCDNAF-REOHCLBHSA-N 0.000 description 1
- CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 1
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 1
- 229930182816 L-glutamine Natural products 0.000 description 1
- AGPKZVBTJJNPAG-WHFBIAKZSA-N L-isoleucine Chemical compound CC[C@H](C)[C@H](N)C(O)=O AGPKZVBTJJNPAG-WHFBIAKZSA-N 0.000 description 1
- 125000000174 L-prolyl group Chemical group [H]N1C([H])([H])C([H])([H])C([H])([H])[C@@]1([H])C(*)=O 0.000 description 1
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
- 102000004856 Lectins Human genes 0.000 description 1
- 108090001090 Lectins Proteins 0.000 description 1
- 108010062867 Lenograstim Proteins 0.000 description 1
- 102100027507 Leucine-rich repeat-containing protein 58 Human genes 0.000 description 1
- GDBQQVLCIARPGH-UHFFFAOYSA-N Leupeptin Natural products CC(C)CC(NC(C)=O)C(=O)NC(CC(C)C)C(=O)NC(C=O)CCCN=C(N)N GDBQQVLCIARPGH-UHFFFAOYSA-N 0.000 description 1
- 102100022172 Ligand-dependent nuclear receptor-interacting factor 1 Human genes 0.000 description 1
- 102000003960 Ligases Human genes 0.000 description 1
- 108090000364 Ligases Proteins 0.000 description 1
- 102000011322 Liprin-beta-1 Human genes 0.000 description 1
- 108050001513 Liprin-beta-1 Proteins 0.000 description 1
- 102100029193 Low affinity immunoglobulin gamma Fc region receptor III-A Human genes 0.000 description 1
- 102100020862 Lymphocyte activation gene 3 protein Human genes 0.000 description 1
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 1
- 102100033143 Lysine-specific demethylase 5D Human genes 0.000 description 1
- 101710105720 Lysine-specific demethylase 5D Proteins 0.000 description 1
- 108010092041 Lysine-tRNA Ligase Proteins 0.000 description 1
- 102100035529 Lysine-tRNA ligase Human genes 0.000 description 1
- 102000001291 MAP Kinase Kinase Kinase Human genes 0.000 description 1
- 108010075647 MAP Kinase Kinase Kinase 4 Proteins 0.000 description 1
- 101710154105 MHC class II regulatory factor RFX1 Proteins 0.000 description 1
- 108010048043 Macrophage Migration-Inhibitory Factors Proteins 0.000 description 1
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
- 102100027329 Malonyl-CoA-acyl carrier protein transacylase, mitochondrial Human genes 0.000 description 1
- 101710137760 Malonyl-CoA-acyl carrier protein transacylase, mitochondrial Proteins 0.000 description 1
- 229930195725 Mannitol Natural products 0.000 description 1
- 101710204291 Melanoma-associated antigen 4 Proteins 0.000 description 1
- 102000012750 Membrane Glycoproteins Human genes 0.000 description 1
- 108010090054 Membrane Glycoproteins Proteins 0.000 description 1
- 108010085747 Methylmalonyl-CoA Decarboxylase Proteins 0.000 description 1
- 102100025298 Mitochondrial-processing peptidase subunit beta Human genes 0.000 description 1
- 101710164333 Mitogen-activated protein kinase kinase kinase 4 Proteins 0.000 description 1
- 108030005453 Mitogen-activated protein kinase kinase kinases Proteins 0.000 description 1
- 102100025275 Monocarboxylate transporter 3 Human genes 0.000 description 1
- 102100035877 Monocyte differentiation antigen CD14 Human genes 0.000 description 1
- 108090001099 Multi drug resistance-associated proteins Proteins 0.000 description 1
- 102000004855 Multi drug resistance-associated proteins Human genes 0.000 description 1
- 241000699660 Mus musculus Species 0.000 description 1
- 101100165237 Mus musculus Bcor gene Proteins 0.000 description 1
- 101001034845 Mus musculus Interferon-induced transmembrane protein 3 Proteins 0.000 description 1
- 101100272228 Mus musculus Pik3ap1 gene Proteins 0.000 description 1
- 101000983164 Mus musculus Proliferation-associated protein 2G4 Proteins 0.000 description 1
- 101000964426 Mus musculus Zinc finger and BTB domain-containing protein 14 Proteins 0.000 description 1
- 102000003505 Myosin Human genes 0.000 description 1
- 108060008487 Myosin Proteins 0.000 description 1
- 101710103757 Myosin heavy chain, skeletal muscle Proteins 0.000 description 1
- 108700026495 N-Myc Proto-Oncogene Proteins 0.000 description 1
- 108700025784 N-myc downstream-regulated gene 1 Proteins 0.000 description 1
- 102100030124 N-myc proto-oncogene protein Human genes 0.000 description 1
- 108010071380 NF-E2-Related Factor 1 Proteins 0.000 description 1
- 101150083560 NONO gene Proteins 0.000 description 1
- 108010025020 Nerve Growth Factor Proteins 0.000 description 1
- 102000007072 Nerve Growth Factors Human genes 0.000 description 1
- 102100023305 Nesprin-2 Human genes 0.000 description 1
- 101710202339 Nesprin-2 Proteins 0.000 description 1
- 102100031903 Neudesin Human genes 0.000 description 1
- 101710090805 Neudesin Proteins 0.000 description 1
- 101710117733 Neurogenic locus notch homolog protein 4 Proteins 0.000 description 1
- 108010021487 Nitric Oxide Synthase Proteins 0.000 description 1
- 102100028083 NmrA-like family domain-containing protein 1 Human genes 0.000 description 1
- 108050000252 Nuclear pore complex protein NUP98-NUP96 Proteins 0.000 description 1
- 102100032226 Nuclear pore complex protein Nup205 Human genes 0.000 description 1
- 101710171042 Nuclear pore complex protein Nup205 Proteins 0.000 description 1
- 102100028470 Nuclear receptor subfamily 2 group C member 1 Human genes 0.000 description 1
- 101710139277 Nucleoporin nup107 Proteins 0.000 description 1
- 102100035644 Olfactory receptor 8G5 Human genes 0.000 description 1
- 101710147088 Olfactory receptor 8G5 Proteins 0.000 description 1
- 102000002512 Orexin Human genes 0.000 description 1
- 102100037588 Orexin receptor type 2 Human genes 0.000 description 1
- 101710116989 Orexin receptor type 2 Proteins 0.000 description 1
- 102000052812 Ornithine decarboxylases Human genes 0.000 description 1
- 241000283973 Oryctolagus cuniculus Species 0.000 description 1
- 101000843120 Oryza sativa subsp. japonica Very-long-chain (3R)-3-hydroxyacyl-CoA dehydratase PASTICCINO 2A Proteins 0.000 description 1
- 101000843117 Oryza sativa subsp. japonica Very-long-chain (3R)-3-hydroxyacyl-CoA dehydratase PASTICCINO 2B Proteins 0.000 description 1
- 101710128268 Oxidoreductase HTATIP2 Proteins 0.000 description 1
- 102100032163 Oxysterol-binding protein 1 Human genes 0.000 description 1
- 102100025661 PDZ domain-containing protein 11 Human genes 0.000 description 1
- 101710153596 PDZ domain-containing protein 11 Proteins 0.000 description 1
- UBXIJOJXUFYNRG-RJKBCLGNSA-N PIP[3'](17:0/20:4(5Z,8Z,11Z,14Z)) Chemical compound CCCCC\C=C/C\C=C/C\C=C/C\C=C/CCCC(=O)O[C@H](COC(=O)CCCCCCCCCCCCCCCC)COP(O)(=O)O[C@H]1C(O)C(O)C(O)[C@@H](OP(O)(O)=O)C1O UBXIJOJXUFYNRG-RJKBCLGNSA-N 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- 241001494479 Pecora Species 0.000 description 1
- 102000035195 Peptidases Human genes 0.000 description 1
- 108091005804 Peptidases Proteins 0.000 description 1
- 108010068204 Peptide Elongation Factors Proteins 0.000 description 1
- 102000002508 Peptide Elongation Factors Human genes 0.000 description 1
- 108010055817 Peptide-N4-(N-acetyl-beta-glucosaminyl) Asparagine Amidase Proteins 0.000 description 1
- 102000000447 Peptide-N4-(N-acetyl-beta-glucosaminyl) Asparagine Amidase Human genes 0.000 description 1
- 101710125432 Periodic tryptophan protein 2 Proteins 0.000 description 1
- 102100032287 Phosphatidylinositide phosphatase SAC2 Human genes 0.000 description 1
- 101710149053 Phosphatidylinositide phosphatase SAC2 Proteins 0.000 description 1
- 102100036687 PiggyBac transposable element-derived protein 3 Human genes 0.000 description 1
- 102100036138 Piwi-like protein 3 Human genes 0.000 description 1
- 206010035226 Plasma cell myeloma Diseases 0.000 description 1
- 101710081133 Plastin-3 Proteins 0.000 description 1
- 102100033008 Poly(U)-binding-splicing factor PUF60 Human genes 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- 102100037450 Potassium voltage-gated channel subfamily A member 7 Human genes 0.000 description 1
- 101000621511 Potato virus M (strain German) RNA silencing suppressor Proteins 0.000 description 1
- 101710163243 Probable ATP-dependent RNA helicase DDX27 Proteins 0.000 description 1
- 101710163237 Probable ATP-dependent RNA helicase ddx31 Proteins 0.000 description 1
- 101710187711 Probable JmjC domain-containing histone demethylation protein 2C Proteins 0.000 description 1
- 102100038289 Probable methyltransferase-like protein 23 Human genes 0.000 description 1
- 101710115782 Proline-tRNA ligase Proteins 0.000 description 1
- 101710180724 Propionyl-CoA carboxylase beta chain Proteins 0.000 description 1
- 239000004365 Protease Substances 0.000 description 1
- 102100040638 Protein AF-17 Human genes 0.000 description 1
- 101710138658 Protein K12 Proteins 0.000 description 1
- 102100025037 Protein Mis18-alpha Human genes 0.000 description 1
- 108010076504 Protein Sorting Signals Proteins 0.000 description 1
- 102100034784 Protein TANC2 Human genes 0.000 description 1
- 102000002727 Protein Tyrosine Phosphatase Human genes 0.000 description 1
- 102000052575 Proto-Oncogene Human genes 0.000 description 1
- 108700020978 Proto-Oncogene Proteins 0.000 description 1
- 108091034057 RNA (poly(A)) Proteins 0.000 description 1
- 102000015097 RNA Splicing Factors Human genes 0.000 description 1
- 108010039259 RNA Splicing Factors Proteins 0.000 description 1
- 101710133282 RNA-binding protein 1 Proteins 0.000 description 1
- 101710205961 RNA-binding protein 34 Proteins 0.000 description 1
- 102100025870 RNA-binding protein 34 Human genes 0.000 description 1
- 239000012979 RPMI medium Substances 0.000 description 1
- 102100022836 Rab-like protein 2B Human genes 0.000 description 1
- 101710153402 Rab-like protein 2B Proteins 0.000 description 1
- 102000003901 Ras GTPase-activating proteins Human genes 0.000 description 1
- 108090000231 Ras GTPase-activating proteins Proteins 0.000 description 1
- 102100034418 Ras GTPase-activating-like protein IQGAP2 Human genes 0.000 description 1
- 101710156978 Ras-like protein Proteins 0.000 description 1
- 102100021586 Ras-like protein family member 11A Human genes 0.000 description 1
- 101710137342 Ras-related protein Rab-27A Proteins 0.000 description 1
- 102100038474 Ras-related protein Rab-3D Human genes 0.000 description 1
- 101710113866 Ras-related protein Rab-3D Proteins 0.000 description 1
- 102100029554 RasGAP-activating-like protein 1 Human genes 0.000 description 1
- 108050004019 RasGAP-activating-like protein 1 Proteins 0.000 description 1
- 101100372762 Rattus norvegicus Flt1 gene Proteins 0.000 description 1
- 102100030086 Receptor tyrosine-protein kinase erbB-2 Human genes 0.000 description 1
- 102000007056 Recombinant Fusion Proteins Human genes 0.000 description 1
- 108010008281 Recombinant Fusion Proteins Proteins 0.000 description 1
- 102100030813 Regulator of G-protein signaling protein-like Human genes 0.000 description 1
- 102100034469 Regulator of telomere elongation helicase 1 Human genes 0.000 description 1
- 108050003886 Regulator of telomere elongation helicase 1 Proteins 0.000 description 1
- 108010030933 Regulatory Factor X1 Proteins 0.000 description 1
- 208000006265 Renal cell carcinoma Diseases 0.000 description 1
- 102000018780 Replication Protein A Human genes 0.000 description 1
- 108010027643 Replication Protein A Proteins 0.000 description 1
- 108091027981 Response element Proteins 0.000 description 1
- 108010071012 Retinoblastoma-Binding Protein 1 Proteins 0.000 description 1
- 102100027663 Rho GTPase-activating protein 12 Human genes 0.000 description 1
- 101710110386 Rho GTPase-activating protein 12 Proteins 0.000 description 1
- 102000006382 Ribonucleases Human genes 0.000 description 1
- 108010083644 Ribonucleases Proteins 0.000 description 1
- 101710158139 Ribosomal L1 domain-containing protein 1 Proteins 0.000 description 1
- 101710168587 Roundabout homolog 3 Proteins 0.000 description 1
- 108010012219 Ryanodine Receptor Calcium Release Channel Proteins 0.000 description 1
- 101710170697 Ryanodine receptor 2 Proteins 0.000 description 1
- 102100035214 SEC14-like protein 1 Human genes 0.000 description 1
- 101710188105 SEC14-like protein 1 Proteins 0.000 description 1
- 238000010847 SEQUEST Methods 0.000 description 1
- 102000037054 SLC-Transporter Human genes 0.000 description 1
- 108091006207 SLC-Transporter Proteins 0.000 description 1
- 108091006615 SLC10A5 Proteins 0.000 description 1
- 108091006607 SLC16A8 Proteins 0.000 description 1
- 108091006700 SLC24A2 Proteins 0.000 description 1
- 102100037599 SPARC Human genes 0.000 description 1
- 108010076622 SS-A antigen Proteins 0.000 description 1
- 108010017324 STAT3 Transcription Factor Proteins 0.000 description 1
- 102100030571 STE20-like serine/threonine-protein kinase Human genes 0.000 description 1
- 101710157230 STE20-like serine/threonine-protein kinase Proteins 0.000 description 1
- 102100022866 SUMO-interacting motif-containing protein 1 Human genes 0.000 description 1
- 240000004808 Saccharomyces cerevisiae Species 0.000 description 1
- 101000898339 Saccharomyces cerevisiae (strain ATCC 204508 / S288c) Eukaryotic peptide chain release factor GTP-binding subunit Proteins 0.000 description 1
- 101000997749 Saccharomyces cerevisiae (strain ATCC 204508 / S288c) Intrastrand cross-link recognition protein Proteins 0.000 description 1
- 101001050208 Saccharomyces cerevisiae (strain ATCC 204508 / S288c) Putative ATP-dependent RNA helicase ECM32 Proteins 0.000 description 1
- 102100030057 Seizure protein 6 homolog Human genes 0.000 description 1
- 102100037548 Semaphorin-6D Human genes 0.000 description 1
- 101710199476 Semaphorin-6D Proteins 0.000 description 1
- 102000017500 Septin 2 Human genes 0.000 description 1
- 108050005721 Septin 2 Proteins 0.000 description 1
- 102100032764 Septin-2 Human genes 0.000 description 1
- 101710202841 Serine/threonine-protein kinase 2 Proteins 0.000 description 1
- 101710091457 Serine/threonine-protein kinase Nek4 Proteins 0.000 description 1
- 102100032771 Serine/threonine-protein kinase SIK1 Human genes 0.000 description 1
- 102000008847 Serpin Human genes 0.000 description 1
- 108050000761 Serpin Proteins 0.000 description 1
- 108010071390 Serum Albumin Proteins 0.000 description 1
- 102000007562 Serum Albumin Human genes 0.000 description 1
- 102100024040 Signal transducer and activator of transcription 3 Human genes 0.000 description 1
- 108020004682 Single-Stranded DNA Proteins 0.000 description 1
- 108020003224 Small Nucleolar RNA Proteins 0.000 description 1
- 102000042773 Small Nucleolar RNA Human genes 0.000 description 1
- 102100021731 Sodium/bile acid cotransporter 5 Human genes 0.000 description 1
- 102100031998 Sodium/potassium/calcium exchanger 2 Human genes 0.000 description 1
- 101710182512 Sorting nexin-14 Proteins 0.000 description 1
- 102100029598 Sorting nexin-14 Human genes 0.000 description 1
- 102100038650 Sorting nexin-4 Human genes 0.000 description 1
- 101710103886 Sorting nexin-4 Proteins 0.000 description 1
- 108010012451 Sp4 Transcription Factor Proteins 0.000 description 1
- 101710109667 Spectrin beta chain Proteins 0.000 description 1
- 101710147970 Spermatogenesis-associated protein 7 Proteins 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- 229930182558 Sterol Natural products 0.000 description 1
- 229930006000 Sucrose Natural products 0.000 description 1
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
- 101710091276 Sulfiredoxin-1 Proteins 0.000 description 1
- 102000004896 Sulfotransferases Human genes 0.000 description 1
- 108090001033 Sulfotransferases Proteins 0.000 description 1
- 102100038648 Synaptogyrin-3 Human genes 0.000 description 1
- 101710152208 Synaptogyrin-3 Proteins 0.000 description 1
- 102100033920 Synemin Human genes 0.000 description 1
- 108700005078 Synthetic Genes Proteins 0.000 description 1
- 102100029454 T cell receptor alpha chain MC.7.G5 Human genes 0.000 description 1
- 230000005867 T cell response Effects 0.000 description 1
- 102100029848 T-box transcription factor TBX18 Human genes 0.000 description 1
- 101710141056 T-box transcription factor TBX18 Proteins 0.000 description 1
- 102100036977 Talin-1 Human genes 0.000 description 1
- 101710142287 Talin-1 Proteins 0.000 description 1
- 102100024842 Taste receptor type 2 member 3 Human genes 0.000 description 1
- 101710129397 Taste receptor type 2 member 3 Proteins 0.000 description 1
- 101710149352 Taste receptor type 2 member 40 Proteins 0.000 description 1
- 108010017842 Telomerase Proteins 0.000 description 1
- 108020005038 Terminator Codon Proteins 0.000 description 1
- 102000002933 Thioredoxin Human genes 0.000 description 1
- 102100031344 Thioredoxin-interacting protein Human genes 0.000 description 1
- 102100029529 Thrombospondin-2 Human genes 0.000 description 1
- IQFYYKKMVGJFEH-XLPZGREQSA-N Thymidine Chemical compound O=C1NC(=O)C(C)=CN1[C@@H]1O[C@H](CO)[C@@H](O)C1 IQFYYKKMVGJFEH-XLPZGREQSA-N 0.000 description 1
- 102100026260 Titin Human genes 0.000 description 1
- 102100031996 Tolloid-like protein 1 Human genes 0.000 description 1
- 101710118137 Tolloid-like protein 1 Proteins 0.000 description 1
- 102100035330 Transmembrane 6 superfamily member 2 Human genes 0.000 description 1
- 101710140337 Transmembrane 6 superfamily member 2 Proteins 0.000 description 1
- 101710193299 Transmembrane channel-like protein Proteins 0.000 description 1
- 102100032041 Transmembrane channel-like protein 4 Human genes 0.000 description 1
- 102100030646 Trichohyalin-like protein 1 Human genes 0.000 description 1
- 108700016206 Tryptophan-tRNA ligases Proteins 0.000 description 1
- 108090000704 Tubulin Proteins 0.000 description 1
- 102000004243 Tubulin Human genes 0.000 description 1
- 102100036111 Tubulin-tyrosine ligase-like protein 12 Human genes 0.000 description 1
- 108050008454 Tubulin-tyrosine ligase-like protein 12 Proteins 0.000 description 1
- 108060008683 Tumor Necrosis Factor Receptor Proteins 0.000 description 1
- 102100040247 Tumor necrosis factor Human genes 0.000 description 1
- 108050002568 Tumor necrosis factor ligand superfamily member 6 Proteins 0.000 description 1
- 101800001213 Tumor necrosis factor ligand superfamily member 6, membrane form Proteins 0.000 description 1
- 102400000086 Tumor necrosis factor ligand superfamily member 6, membrane form Human genes 0.000 description 1
- 108700031758 U1A Proteins 0.000 description 1
- 102100040099 U3 small nucleolar RNA-associated protein 14 homolog A Human genes 0.000 description 1
- 102100037934 U3 small nucleolar RNA-associated protein 6 homolog Human genes 0.000 description 1
- 108091026822 U6 spliceosomal RNA Proteins 0.000 description 1
- 101710109023 UBX domain-containing protein 2 Proteins 0.000 description 1
- 101710109022 UBX domain-containing protein 4 Proteins 0.000 description 1
- 102100031308 UBX domain-containing protein 4 Human genes 0.000 description 1
- 101710176474 UDP-N-acetylglucosamine pyrophosphorylase Proteins 0.000 description 1
- 102100039920 Ubiquitin carboxyl-terminal hydrolase 20 Human genes 0.000 description 1
- 101710091008 Ubiquitin carboxyl-terminal hydrolase 20 Proteins 0.000 description 1
- 102000003431 Ubiquitin-Conjugating Enzyme Human genes 0.000 description 1
- 108060008747 Ubiquitin-Conjugating Enzyme Proteins 0.000 description 1
- 102100038064 Uncharacterized protein C4orf36 Human genes 0.000 description 1
- 108010073929 Vascular Endothelial Growth Factor A Proteins 0.000 description 1
- 102000009484 Vascular Endothelial Growth Factor Receptors Human genes 0.000 description 1
- 108010034265 Vascular Endothelial Growth Factor Receptors Proteins 0.000 description 1
- 102000005789 Vascular Endothelial Growth Factors Human genes 0.000 description 1
- 108010019530 Vascular Endothelial Growth Factors Proteins 0.000 description 1
- 102100028983 Vascular endothelial zinc finger 1 Human genes 0.000 description 1
- 241000710959 Venezuelan equine encephalitis virus Species 0.000 description 1
- 101900253716 Vinculin (isoform 2) Proteins 0.000 description 1
- 102300041335 Vinculin isoform 2 Human genes 0.000 description 1
- 108010093528 Wiskott Aldrich Syndrome protein Proteins 0.000 description 1
- 102100023034 Wiskott-Aldrich syndrome protein Human genes 0.000 description 1
- 108700020985 Wnt-3 Proteins 0.000 description 1
- 102000052549 Wnt-3 Human genes 0.000 description 1
- 102100025377 Zinc finger and BTB domain-containing protein 5 Human genes 0.000 description 1
- 101710160649 Zinc finger and BTB domain-containing protein 5 Proteins 0.000 description 1
- 102100028453 Zinc finger protein 318 Human genes 0.000 description 1
- 101710146934 Zinc finger protein 318 Proteins 0.000 description 1
- MMWCIQZXVOZEGG-HOZKJCLWSA-N [(1S,2R,3S,4S,5R,6S)-2,3,5-trihydroxy-4,6-diphosphonooxycyclohexyl] dihydrogen phosphate Chemical compound O[C@H]1[C@@H](O)[C@H](OP(O)(O)=O)[C@@H](OP(O)(O)=O)[C@H](O)[C@H]1OP(O)(O)=O MMWCIQZXVOZEGG-HOZKJCLWSA-N 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 230000003213 activating effect Effects 0.000 description 1
- 102000035181 adaptor proteins Human genes 0.000 description 1
- 108091005764 adaptor proteins Proteins 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 230000000996 additive effect Effects 0.000 description 1
- 210000001789 adipocyte Anatomy 0.000 description 1
- 230000000240 adjuvant effect Effects 0.000 description 1
- 239000000443 aerosol Substances 0.000 description 1
- 239000000556 agonist Substances 0.000 description 1
- 230000000735 allogeneic effect Effects 0.000 description 1
- 150000001408 amides Chemical class 0.000 description 1
- BFNBIHQBYMNNAN-UHFFFAOYSA-N ammonium sulfate Chemical compound N.N.OS(O)(=O)=O BFNBIHQBYMNNAN-UHFFFAOYSA-N 0.000 description 1
- 229910052921 ammonium sulfate Inorganic materials 0.000 description 1
- 238000012870 ammonium sulfate precipitation Methods 0.000 description 1
- 235000011130 ammonium sulphate Nutrition 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 238000005571 anion exchange chromatography Methods 0.000 description 1
- 150000001450 anions Chemical class 0.000 description 1
- 230000005875 antibody response Effects 0.000 description 1
- 239000007900 aqueous suspension Substances 0.000 description 1
- 125000003118 aryl group Chemical group 0.000 description 1
- 239000005441 aurora Substances 0.000 description 1
- 230000000599 auto-anti-genic effect Effects 0.000 description 1
- 239000011324 bead Substances 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- DRTQHJPVMGBUCF-PSQAKQOGSA-N beta-L-uridine Natural products O[C@H]1[C@@H](O)[C@H](CO)O[C@@H]1N1C(=O)NC(=O)C=C1 DRTQHJPVMGBUCF-PSQAKQOGSA-N 0.000 description 1
- 230000001588 bifunctional effect Effects 0.000 description 1
- 238000002306 biochemical method Methods 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 230000008827 biological function Effects 0.000 description 1
- 238000001574 biopsy Methods 0.000 description 1
- 125000005340 bisphosphate group Chemical group 0.000 description 1
- 239000001506 calcium phosphate Substances 0.000 description 1
- 229910000389 calcium phosphate Inorganic materials 0.000 description 1
- 235000011010 calcium phosphates Nutrition 0.000 description 1
- 125000004432 carbon atom Chemical group C* 0.000 description 1
- 230000000747 cardiac effect Effects 0.000 description 1
- 238000005277 cation exchange chromatography Methods 0.000 description 1
- 150000001768 cations Chemical class 0.000 description 1
- 230000022131 cell cycle Effects 0.000 description 1
- 230000005859 cell recognition Effects 0.000 description 1
- 230000036755 cellular response Effects 0.000 description 1
- 239000001913 cellulose Substances 0.000 description 1
- 229920002678 cellulose Polymers 0.000 description 1
- 230000002925 chemical effect Effects 0.000 description 1
- 238000001311 chemical methods and process Methods 0.000 description 1
- BFPSDSIWYFKGBC-UHFFFAOYSA-N chlorotrianisene Chemical compound C1=CC(OC)=CC=C1C(Cl)=C(C=1C=CC(OC)=CC=1)C1=CC=C(OC)C=C1 BFPSDSIWYFKGBC-UHFFFAOYSA-N 0.000 description 1
- 235000012000 cholesterol Nutrition 0.000 description 1
- 102000006697 chromokinesin Human genes 0.000 description 1
- 108010087363 chromokinesin Proteins 0.000 description 1
- 229960002376 chymotrypsin Drugs 0.000 description 1
- 208000029664 classic familial adenomatous polyposis Diseases 0.000 description 1
- 238000010367 cloning Methods 0.000 description 1
- 229940105778 coagulation factor viii Drugs 0.000 description 1
- 230000002281 colonystimulating effect Effects 0.000 description 1
- 230000006957 competitive inhibition Effects 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 238000012790 confirmation Methods 0.000 description 1
- 230000001276 controlling effect Effects 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- UHDGCWIWMRVCDJ-ZAKLUEHWSA-N cytidine Chemical compound O=C1N=C(N)C=CN1[C@H]1[C@H](O)[C@@H](O)[C@H](CO)O1 UHDGCWIWMRVCDJ-ZAKLUEHWSA-N 0.000 description 1
- 230000001461 cytolytic effect Effects 0.000 description 1
- 230000034994 death Effects 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 108010086096 desmuslin Proteins 0.000 description 1
- 239000008121 dextrose Substances 0.000 description 1
- 239000000032 diagnostic agent Substances 0.000 description 1
- 229940039227 diagnostic agent Drugs 0.000 description 1
- 229940124466 diagnostic for cancer Drugs 0.000 description 1
- 235000014113 dietary fatty acids Nutrition 0.000 description 1
- 230000004069 differentiation Effects 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- 230000005750 disease progression Effects 0.000 description 1
- 241001493065 dsRNA viruses Species 0.000 description 1
- 108010037623 eIF-2 Kinase Proteins 0.000 description 1
- 102000010982 eIF-2 Kinase Human genes 0.000 description 1
- 238000000132 electrospray ionisation Methods 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 238000005538 encapsulation Methods 0.000 description 1
- 230000002124 endocrine Effects 0.000 description 1
- 229940066758 endopeptidases Drugs 0.000 description 1
- 239000003623 enhancer Substances 0.000 description 1
- 210000000981 epithelium Anatomy 0.000 description 1
- 229940011871 estrogen Drugs 0.000 description 1
- 239000000262 estrogen Substances 0.000 description 1
- 102000021484 estrogen response element binding proteins Human genes 0.000 description 1
- 108091011064 estrogen response element binding proteins Proteins 0.000 description 1
- 238000012869 ethanol precipitation Methods 0.000 description 1
- 208000021045 exocrine pancreatic carcinoma Diseases 0.000 description 1
- 230000028023 exocytosis Effects 0.000 description 1
- 210000002744 extracellular matrix Anatomy 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 108010052621 fas Receptor Proteins 0.000 description 1
- 102000018823 fas Receptor Human genes 0.000 description 1
- 229930195729 fatty acid Natural products 0.000 description 1
- 239000000194 fatty acid Substances 0.000 description 1
- 150000004665 fatty acids Chemical class 0.000 description 1
- 210000002950 fibroblast Anatomy 0.000 description 1
- 229960004177 filgrastim Drugs 0.000 description 1
- 238000000684 flow cytometry Methods 0.000 description 1
- 239000012737 fresh medium Substances 0.000 description 1
- 102000054078 gamma Catenin Human genes 0.000 description 1
- 108010084448 gamma Catenin Proteins 0.000 description 1
- 102000034356 gene-regulatory proteins Human genes 0.000 description 1
- 108091006104 gene-regulatory proteins Proteins 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 1
- 150000004676 glycans Chemical class 0.000 description 1
- 125000005456 glyceride group Chemical group 0.000 description 1
- 210000003714 granulocyte Anatomy 0.000 description 1
- 239000003324 growth hormone secretagogue Substances 0.000 description 1
- 238000003306 harvesting Methods 0.000 description 1
- 210000003128 head Anatomy 0.000 description 1
- 210000002443 helper t lymphocyte Anatomy 0.000 description 1
- 208000006454 hepatitis Diseases 0.000 description 1
- 231100000283 hepatitis Toxicity 0.000 description 1
- 208000029570 hepatitis D virus infection Diseases 0.000 description 1
- UFFSXJKVKBQEHC-UHFFFAOYSA-N heptafluorobutyric anhydride Chemical class FC(F)(F)C(F)(F)C(F)(F)C(=O)OC(=O)C(F)(F)C(F)(F)C(F)(F)F UFFSXJKVKBQEHC-UHFFFAOYSA-N 0.000 description 1
- 229920000140 heteropolymer Polymers 0.000 description 1
- HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 description 1
- 102000055229 human IL4 Human genes 0.000 description 1
- 102000052622 human IL7 Human genes 0.000 description 1
- 238000004191 hydrophobic interaction chromatography Methods 0.000 description 1
- 238000012872 hydroxylapatite chromatography Methods 0.000 description 1
- 230000001900 immune effect Effects 0.000 description 1
- 230000001024 immunotherapeutic effect Effects 0.000 description 1
- 230000006698 induction Effects 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 108060004006 inositol polyphosphate 5-phosphatase Proteins 0.000 description 1
- 102000030582 inositol polyphosphate 5-phosphatase Human genes 0.000 description 1
- 238000003780 insertion Methods 0.000 description 1
- 230000037431 insertion Effects 0.000 description 1
- 102000028416 insulin-like growth factor binding Human genes 0.000 description 1
- 108091022911 insulin-like growth factor binding Proteins 0.000 description 1
- 230000002452 interceptive effect Effects 0.000 description 1
- 229960003130 interferon gamma Drugs 0.000 description 1
- 239000000543 intermediate Substances 0.000 description 1
- 230000003834 intracellular effect Effects 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 238000007912 intraperitoneal administration Methods 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- PGLTVOMIXTUURA-UHFFFAOYSA-N iodoacetamide Chemical compound NC(=O)CI PGLTVOMIXTUURA-UHFFFAOYSA-N 0.000 description 1
- 150000002500 ions Chemical class 0.000 description 1
- AGPKZVBTJJNPAG-UHFFFAOYSA-N isoleucine Natural products CCC(C)C(N)C(O)=O AGPKZVBTJJNPAG-UHFFFAOYSA-N 0.000 description 1
- 229960000310 isoleucine Drugs 0.000 description 1
- 125000000741 isoleucyl group Chemical group [H]N([H])C(C(C([H])([H])[H])C([H])([H])C([H])([H])[H])C(=O)O* 0.000 description 1
- NLYAJNPCOHFWQQ-UHFFFAOYSA-N kaolin Chemical compound O.O.O=[Al]O[Si](=O)O[Si](=O)O[Al]=O NLYAJNPCOHFWQQ-UHFFFAOYSA-N 0.000 description 1
- BTNMPGBKDVTSJY-UHFFFAOYSA-N keto-phenylpyruvic acid Chemical compound OC(=O)C(=O)CC1=CC=CC=C1 BTNMPGBKDVTSJY-UHFFFAOYSA-N 0.000 description 1
- 210000003734 kidney Anatomy 0.000 description 1
- KAHDONZOCXSKII-NJVVDGNHSA-N kisspeptin Chemical compound C([C@@H](C(=O)N[C@@H](CO)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](C)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCC(N)=O)C(=O)NCC(=O)N[C@@H](C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=1C=CC=CC=1)C(N)=O)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](C)NC(=O)[C@H](CO)NC(=O)[C@H](CC(C)C)NC(=O)CNC(=O)[C@H]1N(CCC1)C(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CO)NC(=O)CNC(=O)[C@H](CO)NC(=O)[C@H](CO)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H]1N(CCC1)C(=O)[C@H]1N(CCC1)C(=O)[C@H]1N(CCC1)C(=O)[C@H](CO)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)CN)[C@@H](C)O)C1=CN=CN1 KAHDONZOCXSKII-NJVVDGNHSA-N 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 239000000787 lecithin Substances 0.000 description 1
- 229940067606 lecithin Drugs 0.000 description 1
- 235000010445 lecithin Nutrition 0.000 description 1
- 239000002523 lectin Substances 0.000 description 1
- 229960002618 lenograstim Drugs 0.000 description 1
- 210000000265 leukocyte Anatomy 0.000 description 1
- GDBQQVLCIARPGH-ULQDDVLXSA-N leupeptin Chemical compound CC(C)C[C@H](NC(C)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@H](C=O)CCCN=C(N)N GDBQQVLCIARPGH-ULQDDVLXSA-N 0.000 description 1
- 108010052968 leupeptin Proteins 0.000 description 1
- 208000019423 liver disease Diseases 0.000 description 1
- 238000011068 loading method Methods 0.000 description 1
- 201000005249 lung adenocarcinoma Diseases 0.000 description 1
- 239000006166 lysate Substances 0.000 description 1
- 125000003588 lysine group Chemical group [H]N([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])(N([H])[H])C(*)=O 0.000 description 1
- 230000002101 lytic effect Effects 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- 238000002826 magnetic-activated cell sorting Methods 0.000 description 1
- 230000014759 maintenance of location Effects 0.000 description 1
- 239000000594 mannitol Substances 0.000 description 1
- 235000010355 mannitol Nutrition 0.000 description 1
- 238000001819 mass spectrum Methods 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 230000023881 membrane protein ectodomain proteolysis Effects 0.000 description 1
- 210000003716 mesoderm Anatomy 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 239000011325 microbead Substances 0.000 description 1
- 230000000813 microbial effect Effects 0.000 description 1
- 238000007799 mixed lymphocyte reaction assay Methods 0.000 description 1
- 230000009149 molecular binding Effects 0.000 description 1
- 210000000066 myeloid cell Anatomy 0.000 description 1
- 201000000050 myeloid neoplasm Diseases 0.000 description 1
- 210000002850 nasal mucosa Anatomy 0.000 description 1
- 239000005445 natural material Substances 0.000 description 1
- 210000002569 neuron Anatomy 0.000 description 1
- 239000003900 neurotrophic factor Substances 0.000 description 1
- 230000003472 neutralizing effect Effects 0.000 description 1
- 210000004882 non-tumor cell Anatomy 0.000 description 1
- 210000000633 nuclear envelope Anatomy 0.000 description 1
- 235000015097 nutrients Nutrition 0.000 description 1
- 235000021313 oleic acid Nutrition 0.000 description 1
- 150000002889 oleic acids Chemical class 0.000 description 1
- 108060005714 orexin Proteins 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 230000003204 osmotic effect Effects 0.000 description 1
- 108010040421 oxysterol binding protein Proteins 0.000 description 1
- 238000012856 packing Methods 0.000 description 1
- IPCSVZSSVZVIGE-UHFFFAOYSA-N palmitic acid group Chemical group C(CCCCCCCCCCCCCCC)(=O)O IPCSVZSSVZVIGE-UHFFFAOYSA-N 0.000 description 1
- 208000008443 pancreatic carcinoma Diseases 0.000 description 1
- 238000004091 panning Methods 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 230000036961 partial effect Effects 0.000 description 1
- 244000052769 pathogen Species 0.000 description 1
- 230000001717 pathogenic effect Effects 0.000 description 1
- 108010091212 pepstatin Proteins 0.000 description 1
- FAXGPCHRFPCXOO-LXTPJMTPSA-N pepstatin A Chemical compound OC(=O)C[C@H](O)[C@H](CC(C)C)NC(=O)[C@H](C)NC(=O)C[C@H](O)[C@H](CC(C)C)NC(=O)[C@H](C(C)C)NC(=O)[C@H](C(C)C)NC(=O)CC(C)C FAXGPCHRFPCXOO-LXTPJMTPSA-N 0.000 description 1
- 238000010647 peptide synthesis reaction Methods 0.000 description 1
- YPJUNDFVDDCYIH-UHFFFAOYSA-N perfluorobutyric acid Chemical compound OC(=O)C(F)(F)C(F)(F)C(F)(F)F YPJUNDFVDDCYIH-UHFFFAOYSA-N 0.000 description 1
- 230000010412 perfusion Effects 0.000 description 1
- 239000008024 pharmaceutical diluent Substances 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- 229940080469 phosphocellulose Drugs 0.000 description 1
- 239000006069 physical mixture Substances 0.000 description 1
- 230000004962 physiological condition Effects 0.000 description 1
- 230000008884 pinocytosis Effects 0.000 description 1
- 239000013600 plasmid vector Substances 0.000 description 1
- 108010049148 plastin Proteins 0.000 description 1
- 210000004910 pleural fluid Anatomy 0.000 description 1
- 208000030761 polycystic kidney disease Diseases 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 210000004896 polypeptide structure Anatomy 0.000 description 1
- 229920001282 polysaccharide Polymers 0.000 description 1
- 239000005017 polysaccharide Substances 0.000 description 1
- 230000004481 post-translational protein modification Effects 0.000 description 1
- 238000011533 pre-incubation Methods 0.000 description 1
- 210000001236 prokaryotic cell Anatomy 0.000 description 1
- 235000019419 proteases Nutrition 0.000 description 1
- 102000021127 protein binding proteins Human genes 0.000 description 1
- 108091011138 protein binding proteins Proteins 0.000 description 1
- 230000030788 protein refolding Effects 0.000 description 1
- 108020000494 protein-tyrosine phosphatase Proteins 0.000 description 1
- 230000017854 proteolysis Effects 0.000 description 1
- 108010033990 rab27 GTP-Binding Proteins Proteins 0.000 description 1
- 102000005912 ran GTP Binding Protein Human genes 0.000 description 1
- 108010005597 ran GTP Binding Protein Proteins 0.000 description 1
- 238000010188 recombinant method Methods 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 231100000628 reference dose Toxicity 0.000 description 1
- 230000034614 regulation of DNA-dependent DNA replication initiation Effects 0.000 description 1
- 239000011347 resin Substances 0.000 description 1
- 229920005989 resin Polymers 0.000 description 1
- 230000002441 reversible effect Effects 0.000 description 1
- 108010033674 rho GTP-Binding Proteins Proteins 0.000 description 1
- 210000003705 ribosome Anatomy 0.000 description 1
- 108091052345 ryanodine receptor (TC 1.A.3.1) family Proteins 0.000 description 1
- CVHZOJJKTDOEJC-UHFFFAOYSA-N saccharin Chemical compound C1=CC=C2C(=O)NS(=O)(=O)C2=C1 CVHZOJJKTDOEJC-UHFFFAOYSA-N 0.000 description 1
- 238000010845 search algorithm Methods 0.000 description 1
- 239000003001 serine protease inhibitor Substances 0.000 description 1
- 230000000405 serological effect Effects 0.000 description 1
- 239000012679 serum free medium Substances 0.000 description 1
- 230000035939 shock Effects 0.000 description 1
- 230000011664 signaling Effects 0.000 description 1
- 210000002027 skeletal muscle Anatomy 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 210000000952 spleen Anatomy 0.000 description 1
- 206010041823 squamous cell carcinoma Diseases 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 238000011146 sterile filtration Methods 0.000 description 1
- 239000008223 sterile water Substances 0.000 description 1
- 230000001954 sterilising effect Effects 0.000 description 1
- 238000004659 sterilization and disinfection Methods 0.000 description 1
- 150000003432 sterols Chemical class 0.000 description 1
- 235000003702 sterols Nutrition 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 150000005846 sugar alcohols Polymers 0.000 description 1
- 238000001356 surgical procedure Methods 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 210000002182 synaptic membrane Anatomy 0.000 description 1
- 210000005050 synemin Anatomy 0.000 description 1
- 108091035539 telomere Proteins 0.000 description 1
- 102000055501 telomere Human genes 0.000 description 1
- 210000003411 telomere Anatomy 0.000 description 1
- 230000002381 testicular Effects 0.000 description 1
- 210000001550 testis Anatomy 0.000 description 1
- 229960000814 tetanus toxoid Drugs 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 108060008226 thioredoxin Proteins 0.000 description 1
- 229940094937 thioredoxin Drugs 0.000 description 1
- 108010060887 thrombospondin 2 Proteins 0.000 description 1
- 238000010361 transduction Methods 0.000 description 1
- 230000026683 transduction Effects 0.000 description 1
- 230000009261 transgenic effect Effects 0.000 description 1
- 230000001052 transient effect Effects 0.000 description 1
- 238000013519 translation Methods 0.000 description 1
- 102000035160 transmembrane proteins Human genes 0.000 description 1
- 108091005703 transmembrane proteins Proteins 0.000 description 1
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
- 102000003298 tumor necrosis factor receptor Human genes 0.000 description 1
- 108010087967 type I signal peptidase Proteins 0.000 description 1
- 108010008314 tyrosine-tubulin Proteins 0.000 description 1
- DRTQHJPVMGBUCF-UHFFFAOYSA-N uracil arabinoside Natural products OC1C(O)C(CO)OC1N1C(=O)NC(=O)C=C1 DRTQHJPVMGBUCF-UHFFFAOYSA-N 0.000 description 1
- 229940045145 uridine Drugs 0.000 description 1
- 102000038650 voltage-gated calcium channel activity Human genes 0.000 description 1
- 108091023044 voltage-gated calcium channel activity Proteins 0.000 description 1
- 102100036538 von Willebrand factor C and EGF domain-containing protein Human genes 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 230000003442 weekly effect Effects 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
- 210000005253 yeast cell Anatomy 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/0005—Vertebrate antigens
- A61K39/0011—Cancer antigens
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- A61K38/18—Growth factors; Growth regulators
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- A61K38/19—Cytokines; Lymphokines; Interferons
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/46—Cellular immunotherapy
- A61K39/461—Cellular immunotherapy characterised by the cell type used
- A61K39/4611—T-cells, e.g. tumor infiltrating lymphocytes [TIL], lymphokine-activated killer cells [LAK] or regulatory T cells [Treg]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/46—Cellular immunotherapy
- A61K39/464—Cellular immunotherapy characterised by the antigen targeted or presented
- A61K39/4643—Vertebrate antigens
- A61K39/4644—Cancer antigens
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/10—Dispersions; Emulsions
- A61K9/127—Liposomes
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
- A61P37/04—Immunostimulants
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/46—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates
- C07K14/47—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/46—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates
- C07K14/47—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals
- C07K14/4701—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals not used
- C07K14/4738—Cell cycle regulated proteins, e.g. cyclin, CDC, INK-CCR
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/46—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates
- C07K14/47—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals
- C07K14/4701—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals not used
- C07K14/4748—Tumour specific antigens; Tumour rejection antigen precursors [TRAP], e.g. MAGE
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/475—Growth factors; Growth regulators
- C07K14/485—Epidermal growth factor [EGF] (urogastrone)
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/705—Receptors; Cell surface antigens; Cell surface determinants
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/705—Receptors; Cell surface antigens; Cell surface determinants
- C07K14/70546—Integrin superfamily
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/705—Receptors; Cell surface antigens; Cell surface determinants
- C07K14/71—Receptors; Cell surface antigens; Cell surface determinants for growth factors; for growth regulators
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N5/00—Undifferentiated human, animal or plant cells, e.g. cell lines; Tissues; Cultivation or maintenance thereof; Culture media therefor
- C12N5/06—Animal cells or tissues; Human cells or tissues
- C12N5/0602—Vertebrate cells
- C12N5/0634—Cells from the blood or the immune system
- C12N5/0636—T lymphocytes
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
- G01N33/574—Immunoassay; Biospecific binding assay; Materials therefor for cancer
- G01N33/57484—Immunoassay; Biospecific binding assay; Materials therefor for cancer involving compounds serving as markers for tumor, cancer, neoplasia, e.g. cellular determinants, receptors, heat shock/stress proteins, A-protein, oligosaccharides, metabolites
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K2039/51—Medicinal preparations containing antigens or antibodies comprising whole cells, viruses or DNA/RNA
- A61K2039/515—Animal cells
- A61K2039/5154—Antigen presenting cells [APCs], e.g. dendritic cells or macrophages
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K2039/51—Medicinal preparations containing antigens or antibodies comprising whole cells, viruses or DNA/RNA
- A61K2039/515—Animal cells
- A61K2039/5158—Antigen-pulsed cells, e.g. T-cells
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K2039/51—Medicinal preparations containing antigens or antibodies comprising whole cells, viruses or DNA/RNA
- A61K2039/52—Bacterial cells; Fungal cells; Protozoal cells
- A61K2039/522—Bacterial cells; Fungal cells; Protozoal cells avirulent or attenuated
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K2039/51—Medicinal preparations containing antigens or antibodies comprising whole cells, viruses or DNA/RNA
- A61K2039/53—DNA (RNA) vaccination
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K2039/80—Vaccine for a specifically defined cancer
- A61K2039/812—Breast
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
Definitions
- the present invention relates generally to the field of immunogens whose structures incorporate polypeptides comprising epitopic peptides derived from proteins expressed by cancer cells and to uses of said immunogens in eliciting cytotoxic T lymphocyte (CTL) responses for the diagnosis, prevention and treatment of cancer, preferably carcinoma, most preferably ovarian carcinoma.
- CTL cytotoxic T lymphocyte
- T cells The mammalian immune system has evolved a variety of mechanisms to protect the host from cancerous cells, an important component of this response being mediated by cells referred to as T cells.
- Cytotoxic T lymphocytes are specialized T cells that function primarily by recognizing and killing cancerous cells or infected cells, but also by secreting soluble molecules referred to as cytokines that can mediate a variety of effects on the immune system.
- MHC-peptide complex which is located on the surface of the cancerous cell.
- MHC (major histocompatibility-complex)-encoded molecules have been subdivided into two types, and are referred to as class I and class II MHC-encoded molecules.
- MHC molecules are referred to as human leukocyte antigens (HLA).
- HLA human leukocyte antigens
- the genes that can be encoded at each of these loci are extremely polymorphic, and thus, different individuals within the population express different class I MHC molecules on the surface of their cells.
- HLA-A1, HLA-A2, HLA-A3, HLA-B7, and HLA-B8 are examples of different class I MHC molecules that can be expressed from these loci.
- the present disclosure involves peptides that are associated with the HLA-A1, HLA-A2, or HLA-A11 molecules, HLA-A1 supertypes, HLA-A2 supertypes, and HLA-A11 supertypes and with the gene and protein that gives rise to these peptides.
- a supertype is a group of HLA molecules that present at least one shared epitope.
- the peptides that associate with the MHC molecules can either be derived from proteins made within the cell, in which case they typically associate with class I MHC molecules (Rock, K. L. and Golde, U., Ann. Rev. Immunol., 17:739-779, (1999)) or they can be derived from proteins that are acquired from outside of the cell, in which case they typically associate with class II MHC molecules (Watts, C., Ann. Rev. Immunol., 15:821-850, (1997)). Peptides that evoke a cancer-specific CTL response most typically associate with class I MHC molecules.
- the peptides that associate with a class I MHC molecule are typically nine amino acids in length, but can vary from a minimum length of eight amino acids to a maximum of fourteen amino acids in length.
- a class I MHC molecule with its bound peptide, or a class II MHC molecule with its bound peptide, is referred to as an MHC-peptide complex.
- antigen processing The process by which intact proteins are degraded into peptides is referred to as antigen processing.
- Two major pathways of antigen processing occur within cells (Rock, K. L. and Golde, U., Ann. Rev. Immunol., 17:739-779, (1999); Watts, C., Ann. Rev. Immunol., 15:821-850, (1997)).
- One pathway which is largely restricted to cells that are antigen presenting cells such as dendritic cells, macrophages, and B cells, degrades proteins that are typically phagocytosed or endocytosed into the cell. Peptides derived in this pathway typically bind to class II MHC molecules.
- a second pathway of antigen processing is present in essentially all cells of the body.
- This second pathway primarily degrades proteins that are made within the cells, and the peptides derived from this pathway primarily bind to class I MHC molecules. It is the peptides from this second pathway of antigen processing that are referred to herein. Antigen processing by this latter pathway involves polypeptide synthesis and proteolysis in the cytoplasm. The peptides produced are then transported into the endoplasmic reticulum of the cell, associate with newly synthesized class I MHC molecules, and the resulting MHC-peptide complexes are then transported to the cell surface. Peptides derived from membrane and secreted proteins have also been identified. In some cases these peptides correspond to the signal sequence of the proteins that are cleaved from the protein by the signal peptidase. In other cases, it is thought that some fraction of the membrane and secreted proteins are transported from the endoplasmic reticulum into the cytoplasm where processing subsequently occurs.
- the peptides are recognized by antigen-specific receptors on CTLs. Mere expression of the class I MHC molecule itself is insufficient to trigger the CTL to kill the target cell if the antigenic peptide is not bound to the class I MHC molecule.
- CTLs Several methods have been developed to identify the peptides recognized by CTL, each method relying on the ability of a CTL to recognize and kill only those cells expressing the appropriate class I MHC molecule with the peptide bound to it (Rosenberg, S. A., Immunity, 10:281-287, (1999)).
- Such peptides can be derived from a non-self source, such as a pathogen (for example, following the infection of a cell by a bacterium or a virus) or from a self-derived protein within a cell, such as a cancerous cell.
- a pathogen for example, following the infection of a cell by a bacterium or a virus
- a self-derived protein within a cell such as a cancerous cell.
- Immunity 10:281-287, (1999) and include: (i) mutated genes; (ii) aberrantly expressed genes such as an alternative open reading frame or through an intron-exon boundary; (iii) normal genes that are selectively expressed in only the tumor and the testis; and (iv) normal differentiation genes that are expressed in the tumor and the normal cellular counterpart.
- the genetic method is an approach in which progressively smaller subsets of cDNA libraries from tumor cells are transfected into cells that express the appropriate MHC molecule but not the tumor-specific epitope.
- the molecular clones encoding T cell epitopes are identified by their ability to reconstitute tumor specific T cell recognition of transfected cells.
- the exact T cell epitope is then identified by a combination of molecular subcloning and the use of synthetic peptides based on the predicted amino acid sequence.
- Such methods are susceptible to inadvertent identification of cross-reacting peptides, and are not capable of identifying important post-translational modifications.
- Motif analysis involves scanning a protein for peptides containing known class I MHC binding motifs, followed by synthesis and assay of the predicted peptides for their ability to be recognized by tumor-specific CTL. This approach requires prior knowledge of the protein from which the peptides are derived. This approach is also greatly hampered by the fact that not all of the predicted peptide epitopes are presented on the surface of a cell (Yewdell, J. W. and Bennink, J. R., Ann. Rev. Immunol., 17:51-88, (1999)), thus additional experimentation is required to determine which of the predicted epitopes is useful.
- the SEREXTM approach relies on using antibodies in the serum of cancer patients to screen cDNA expression libraries for a clone that expresses a protein recognized by the antibody. This methodology presumes that an antibody response will necessarily have developed in the presence of a T cell response, and thus, the identified clone is good candidate to encode a protein that can be recognized by T cells.
- DIRECTM involves a combination of cellular immunology and mass spectrometry.
- This approach involves the actual identification of CTL epitopes by sequencing the naturally occurring peptides associated with class I MHC molecules.
- cells are first lysed in a detergent solution, the peptides associated with the class I MHC molecules are purified, and the peptides fractionated by high performance liquid chromatography (HPLC). The peptides are then used to reconstitute recognition by tumor-specific CTLs on a non-tumor cell expressing the appropriate MHC molecules. Sequencing is readily performed by tandem mass spectrometry (Henderson, R. A. et al., Proc. Natl. Acad.
- Immunization with cancer-derived, class I MHC-encoded molecule-associated peptides, or with a precursor polypeptide or protein that contains the peptide, or with a gene that encodes a polypeptide or protein containing the peptide, are forms of immunotherapy that can be employed in the treatment of cancer. These forms of immunotherapy require that immunogens be identified so that they can be formulated into an appropriate vaccine. Although a variety of cancer-derived antigens have been identified (Rosenberg, S. A., Immunity, 10:281-287, (1999)), not all of these are appropriate for broad-based immunotherapy as the expression of some peptides is limited to the tumor derived from a specific patient.
- class I MHC molecules from which tumor-derived peptides have been discovered is largely restricted to HLA-A2.
- Such peptides would be particularly useful in the treatment of cancer patients who do not express the HLA-A2 molecule, HLA-A1 or HLA-A11 antigens, HLA-A1 supertypes, HLA-A2 supertypes and HLA-A11 supertypes, for example. It is also particularly useful to identify antigenic peptides that are derived from different original proteins, even if the derived peptides associate with the same class I MHC molecule.
- an active immune response can result in the outgrowth of tumor cells that have lost the expression of a particular precursor protein for a given antigenic peptide, it is advantageous to stimulate an immune response against peptides derived from more than one protein, as the chances of the tumor cell losing the expression of both proteins is the multiple of the chances of losing each of the individual proteins.
- the present invention relates to Immunogens comprising polypeptides with amino acid sequences comprising epitopic sequences selected from the sequences of SEQ ID NO: 1-791 and 1514-1533 and which immunogens facilitate a cytotoxic T lymphocyte (CTL)-mediated immune response against cancers.
- CTL cytotoxic T lymphocyte
- the present invention also relates to nucleic acid molecules that encode for the polypeptides and/or the full length proteins from which the polypeptides are derived, of such immunogens, and which can also be used to facilitate an immune response against cancer.
- compositions comprising the immunogen described herein, and polynucleotides that direct the synthesis of such polypeptides, whereby the oligopeptides and polypeptides of such immunogens are capable of inducing a CTL response against cells expressing a protein comprising an epitopic sequence of at least one of SEQ ID NO: 1-791 and 1514-1533.
- the cells are usually cancer cells, preferably carcinoma cells, most preferably ovarian carcinomas expressing such proteins.
- the present invention further relates to polynucleotides comprising the gene coding for a polypeptide of the immunogens disclosed herein.
- the present invention also provides methods that comprise contacting a lymphocyte, especially a CTL, with an immunogen of the invention under conditions that induce a CTL response against a tumor cell, and more specifically against a cancer cell.
- the methods may involve contacting the CTL with the immunogenic peptide in vivo, in which case the peptides, polypeptides, and polynucleotides of the invention are used as vaccines, and will be delivered as a pharmaceutical composition comprising a pharmaceutically acceptable carrier and the immunogen, typically along with an adjuvant or one or more cytokines.
- the immunogens of the present invention can be used to induce a CTL response in vitro.
- the generated CTL can then be introduced into a patient with cancer, more specifically cancer, colorectal carcinoma, ovarian carcinoma, breast carcinoma, lung carcinoma, or prostate carcinoma.
- cancer more specifically cancer, colorectal carcinoma, ovarian carcinoma, breast carcinoma, lung carcinoma, or prostate carcinoma.
- the ability to generate CTL in vitro could serve as a diagnostic for cancer generally, including colorectal carcinoma, ovarian carcinoma, breast carcinoma, lung carcinoma, or prostate carcinoma.
- peptide is used herein to designate a series of amino acid residues, connected one to the other typically by peptide bonds between the alpha-amino and carbonyl groups of the adjacent amino acids.
- the peptides are typically 9 amino acids in length, but can be as short as 8 amino acids in length, and as long as 14 amino acids in length.
- oligopeptide is used herein to designate a series of amino acid residues, connected one to the other typically by peptide bonds between the alpha-amino and carbonyl groups of the adjacent amino acids.
- the length of the oligopeptide is not critical to the invention as long as the correct epitope or epitopes are maintained therein.
- the oligopeptides are typically less than about 30 amino acid residues in length, and greater than about 14 amino acids in length.
- polypeptide designates a series of amino acid residues, connected one to the other typically by peptide bonds between the alpha-amino and carbonyl groups of the adjacent amino acids.
- the length of the polypeptide is not critical to the invention as long as the correct epitopes are maintained.
- the term polypeptide is meant to refer to protein molecules of longer than about 30 residues in length.
- a peptide, oligopeptide, protein, or polynucleotide coding for such a molecule is “immunogenic” (and thus an “immunogen” within the present invention) if it is capable of inducing an immune response.
- immunogenicity is more specifically defined as the ability to induce a CTL-mediated response.
- an “immunogen” would be a molecule that is capable of inducing an immune response, and in the case of the present invention, a molecule capable of inducing a CTL response.
- a T cell “epitope” is a short peptide molecule that binds to a class I or II MHC molecule and that is subsequently recognized by a T cell.
- T cell epitopes that bind to class I MHC molecules are typically 8-14 amino acids in length, and most typically 9 amino acids in length.
- T cell epitopes that bind to class II MHC molecules are typically 12-20 amino acids in length.
- the same T cell epitope may share a common core segment, but differ in the length of the carboxy- and amino-terminal flanking sequences due to the fact that ends of the peptide molecule are not buried in the structure of the class II MHC molecule peptide-binding cleft as they are in the class I MHC molecule peptide-binding cleft.
- HLA-A There are three different genetic loci that encode for class I MHC molecules: HLA-A, HLA-B, and HLA-C.
- HLA-A1, HLA-A2, and HLA-A11 are examples of different class I MHC molecules that can be expressed from these loci.
- the present invention also involves peptides that are associated with HLA-A1 supertypes, HLA-A2 supertypes, and HLA-A11 supertypes.
- a supertype is a group of HLA molecules that present at least one shared epitope.
- MHC molecule peptides that have been found to bind to one member of the MHC allele supertype family (A1 for example) are thought to be likely to bind to other members of the same supertype family (A32 for example; see Table 1, below.
- reference to a DNA sequence includes both single stranded and double stranded DNA.
- specific sequence unless the context indicates otherwise, refers to the single strand DNA of such sequence, the duplex of such sequence with its complement (double stranded DNA) and the complement of such sequence.
- coding region refers to that portion of a gene which either naturally or normally codes for the expression product of that gene in its natural genomic environment, i.e., the region coding in vivo for the native expression product of the gene.
- the coding region can be from a normal, mutated or altered gene, or can even be from a DNA sequence, or gene, wholly synthesized in the laboratory using methods well known to those of skill in the art of DNA synthesis.
- nucleotide sequence refers to a heteropolymer of deoxyribonucleotides.
- the nucleotide sequence encoding for a particular peptide, oligopeptide, or polypeptide may be naturally occurring or they may be synthetically constructed.
- DNA segments encoding the peptides, polypeptides, and proteins of this invention are assembled from cDNA fragments and short oligonucleotide linkers, or from a series of oligonucleotides, to provide a synthetic gene which is capable of being expressed in a recombinant transcriptional unit comprising regulatory elements derived from a microbial or viral operon.
- expression product means that polypeptide or protein that is the natural translation product of the gene and any nucleic acid sequence coding equivalents resulting from genetic code degeneracy and thus coding for the same amino acid(s).
- fragment when referring to a coding sequence, means a portion of DNA comprising less than the complete coding region whose expression product retains essentially the same biological function or activity as the expression product of the complete coding region.
- DNA segment refers to a DNA polymer, in the form of a separate fragment or as a component of a larger DNA construct, which has been derived from DNA isolated at least once in substantially pure form, i.e., free of contaminating endogenous materials and in a quantity or concentration enabling identification, manipulation, and recovery of the segment and its component nucleotide sequences by standard biochemical methods, for example, by using a cloning vector.
- Such segments are provided in the form of an open reading frame uninterrupted by internal nontranslated sequences, or introns, which are typically present in eukaryotic genes. Sequences of non-translated DNA may be present downstream from the open reading frame, where the same do not interfere with manipulation or expression of the coding regions.
- primer means a short nucleic acid sequence that is paired with one strand of DNA and provides a free 3′0H end at which a DNA polymerase starts synthesis of a deoxyribonucleotide chain.
- promoter means a region of DNA involved in binding of RNA polymerase to initiate transcription.
- ORF open reading frame
- isolated means that the material is removed from its original environment (e.g., the natural environment if it is naturally occurring).
- a naturally-occurring polynucleotide or polypeptide present in a living animal is not isolated, but the same polynucleotide or polypeptide, separated from some or all of the coexisting materials in the natural system, is isolated.
- Such polynucleotides could be part of a vector and/or such polynucleotides or polypeptides could be part of a composition, and still be isolated in that such vector or composition is not part of its natural environment.
- polynucleotides, and recombinant or immunogenic polypeptides, disclosed in accordance with the present invention may also be in “purified” form.
- the term “purified” does not require absolute purity; rather, it is intended as a relative definition, and can include preparations that are highly purified or preparations that are only partially purified, as those terms are understood by those of skill in the relevant art.
- individual clones isolated from a cDNA library have been conventionally purified to electrophoretic homogeneity. Purification of starting material or natural material to at least one order of magnitude, preferably two or three orders, and more preferably four or five orders of magnitude is expressly contemplated.
- the claimed polypeptide which has a purity of preferably 0.001%, or at least 0.01% or 0.1%; and even desirably 1% by weight or greater is expressly contemplated.
- nucleic acids and polypeptide expression products disclosed according to the present invention may be in “enriched form.”
- enriched means that the concentration of the material is at least about 2, 5, 10, 100, or 1000 times its natural concentration (for example), advantageously 0.01%, by weight, preferably at least about 0.1% by weight. Enriched preparations of about 0.5%, 1%, 5%, 10%, and 20% by weight are also contemplated.
- sequences, constructs, vectors, clones, and other materials comprising the present invention can advantageously be in enriched or isolated form.
- active fragment means a fragment that generates an immune response (i.e., has immunogenic activity) when administered, alone or optionally with a suitable adjuvant, to an animal, such as a mammal, for example, a rabbit or a mouse, and also including a human, such immune response taking the form of stimulating a CTL response within the recipient animal, such as a human.
- an animal such as a mammal, for example, a rabbit or a mouse
- the “active fragment” may also be used to induce a CTL response in vitro.
- portion when used in relation to polypeptides, refer to a continuous sequence of residues, such as amino acid residues, which sequence forms a subset of a larger sequence.
- residues such as amino acid residues
- fragment when used in relation to polypeptides, refer to a continuous sequence of residues, such as amino acid residues, which sequence forms a subset of a larger sequence.
- the oligopeptides resulting from such treatment would represent portions, segments or fragments of the starting polypeptide.
- any such fragment will necessarily contain as part of its amino acid sequence a segment, fragment or portion, that is substantially identical, if not exactly identical, to a sequence of SEQ ID NO: 792-1513, which correspond to the naturally occurring, or “parent” proteins of the SEQ ID NO: 1-791 and 1514-1533.
- such terms refer to the products produced by treatment of said polynucleotides with any of the common endonucleases.
- the term “percent identity” or “percent identical,” when referring to a sequence, means that a sequence is compared to a claimed or described sequence after alignment of the sequence to be compared (the “Compared Sequence”) with the described or claimed sequence (the “Reference Sequence”). The Percent Identity is then determined according to the following formula:
- C is the number of differences between the Reference Sequence and the Compared Sequence over the length of alignment between the Reference Sequence and the Compared Sequence wherein (i) each base or amino acid in the Reference Sequence that does not have a corresponding aligned base or amino acid in the Compared Sequence and (ii) each gap in the Reference Sequence and (iii) each aligned base or amino acid in the Reference Sequence that is different from an aligned base or amino acid in the Compared Sequence, constitutes a difference; and R is the number of bases or amino acids in the Reference Sequence over the length of the alignment with the Compared Sequence with any gap created in the Reference Sequence also being counted as a base or amino acid.
- the Compared Sequence has the specified minimum percent identity to the Reference Sequence even though alignments may exist in which the herein above calculated Percent Identity is less than the specified Percent Identity.
- the present invention relates generally to immunogens and immunogenic compositions, and methods of use therefore, for the prevention, treatment, and diagnosis of cancer, especially carcinomas, including ovarian carcinomas.
- immunogens comprising proteins or polypeptides whose amino acid sequences comprises one or more epitopic oligopeptides with sequences selected from the group SEQ ID NO: 1-791 and 1514-1533.
- the invention further relates to polynucleotides that can be used to stimulate a CTL response against cancer, and more specifically carcinoma, especially ovarian carcinomas.
- oligopeptide sequences with amino acid sequences shown in SEQ ID NO: 1-791 and 1514-1533, which represent epitopic peptides (i.e. immunogenic oligopeptide sequences) of at least about 8 amino acids in length, preferably about 9 amino acids in length (i.e., nonapeptides), and no longer than about 10 amino acids in length and present as part of a larger structure, such as a polypeptide or full length protein.
- epitopic peptides i.e. immunogenic oligopeptide sequences
- amino acid sequences shown in SEQ ID NO: 1-791 and 1514-1533 represent epitopic peptides (i.e. immunogenic oligopeptide sequences) of at least about 8 amino acids in length, preferably about 9 amino acids in length (i.e., nonapeptides), and no longer than about 10 amino acids in length and present as part of a larger structure, such as a polypeptide or full length protein.
- polypeptides forming the immunogens of the present invention have amino acid sequences that comprise at least one stretch, possibly two, three, four, or more stretches of about 8 to 10 residues in length and which stretches differ in amino acid sequence from the sequences of SEQ ID NO: 1-791 and 1514-1533 by no more than about 1 amino acid residue, preferably a conservative amino acid residue, especially amino acids of the same general chemical character, such as where they are hydrophobic amino acids.
- Said polypeptides can be of any desired length so long as they have immunogenic activity in that they are able, under a given set of desirable conditions, to elicit in vitro or in vivo the activation of cytotoxic T lymphocytes (CTLs) (i.e., a CTL response) against a presentation of a cancer specific protein, especially a carcinoma or sarcoma specific protein, most especially MAGE D, MAGE 4, MFG-E8 or human retinoblastoma-like protein, especially when such proteins are presented along with MHC-1 proteins, such as where said proteins are presented in vitro or in vivo by an antigen presenting cell (APC).
- CTLs cytotoxic T lymphocytes
- APC antigen presenting cell
- the proteins and polypeptides forming the immunogens of the present invention can be naturally occurring or may be synthesized chemically.
- the polypeptides may comprise at least one of SEQ ID NO: 792-1513.
- the present invention is also directed to an isolated polypeptide, especially one having immunogenic activity, the sequence of which comprises within it one or more stretches comprising any 2 or more of the sequences of SEQ ID NO: 1-791 and 1514-1533 and in any relative quantities and wherein said sequences may differ by one amino acid residues from the sequences of SEQ ID NO: 1-791 and 1514-1533 in any given stretch of 8 to 10 amino acid residues.
- such polypeptide may contain as part of its amino acid sequence, nonapeptide fragments having up to 8 amino acids identical to a sequence of SEQ ID NO: 1-4 such that the polypeptide comprises, in a specific embodiment, 2 segments with at least 8 residues identical to SEQ ID NO: 1 and one segment with at least 8 residues identical to SEQ ID NO: 3.
- other combinations and permutations of the epitopic sequences disclosed herein may be part of an immunogen of the present invention or of such a polypeptide so long as any such polypeptide comprises at least 2 such epitopes, whether such epitopes are different or the same.
- a polypeptide of the present invention may comprise 2 copies of the sequence of SEQ ID NO: 2 at some point or points within its length.
- any combinations and permutations of the epitopes disclosed herein, as long as they are present at least two in number in such polypeptides, are expressly contemplated.
- SEQ ID NO: 792-1513 are polypeptides that comprise at least one of SEQ ID NO: 1-791 and 1514-1533.
- Oligopeptides as disclosed herein may themselves be prepared by methods well known to those skilled in the art. (Grant, G. A., Synthetic Peptides: A User's Guide, 1992, W. H. Freeman and Company, New York; Coligan, J. E. et al, Current Protocols in Protein Science, 1999, John Wiley & Sons, Inc., New York).
- the proteins and polypeptides forming the immunogens of the present invention may also comprise one or more other immunogenic amino acid stretches known to be associated with cancer, and more specifically with carcinomas and melanomas, including colorectal carcinoma, ovarian carcinoma, breast carcinoma, lung carcinoma, or prostate carcinoma, and which may stimulate a CTL response whereby the immunogenic peptides associate with HLA-A1 or HLA-A11, or HLA-A2, or another class I MHC (i.e., MHC-1) molecule.
- MHC class I MHC
- the immunogens of the present invention can be in the form of a composition of one or more of the different immunogens and wherein each immunogen is present in any desired relative abundance.
- Such compositions can be homogeneous or heterogeneous with respect to the individual immunogenic peptide components present therein, having only one or more than one of such peptides.
- oligopeptides and polypeptides useful in practicing the present invention may be derived by fractionation of naturally occurring proteins by methods such as protease treatment, or they may be produced by recombinant or synthetic methodologies that are well known and clear to the skilled artisan (Ausubel, F. M. et al, Current Protocols in Molecular Biology, 1999, John Wiley & Sons, Inc., New York; Coligan, J. E. et al, Current Protocols in Protein Science, 1999, John Wiley & Sons, Inc., New York; Molecular Cloning: A Laboratory Manual, 1989, Cold Spring Harbor Laboratory Press, Cold Spring Harbor).
- the polypeptide may comprise a recombinant or synthetic polypeptide that comprises at least one of SEQ ID NO:1-791 and 1514-1533 which sequences may also be present in multiple copies.
- oligopeptides and polypeptides of the present invention may have one, two, three, or more such immunogenic peptides within the amino acid sequence of said oligopeptides and polypeptides, and said immunogenic peptides, or epitopes, may be the same or may be different, or may have any number of such sequences wherein some of them are identical to each other in amino acid sequence while others within the same polypeptide sequence are different from each other and said epitopic sequences may occur in any order within said immunogenic polypeptide sequence.
- immunogens of the present invention may affect relative immunogenic activity.
- immunogens of the present invention may comprise more than one protein comprising the amino acid sequences disclosed herein.
- Such polypeptides may be part of a single composition or may themselves be covalently or non-covalently linked to each other.
- the immunogenic peptides disclosed herein may also be linked directly to, or through a spacer or linker to: an immunogenic carrier such as serum albumin, tetanus toxoid, keyhole limpet hemocyanin, dextran, or a recombinant virus particle; an immunogenic peptide known to stimulate a T helper cell type immune response; a cytokine such as interferon gamma or GMCSF; a targeting agent such as an antibody or receptor ligand; a stabilizing agent such as a lipid; or a conjugate of a plurality of epitopes to a branched lysine core structure, such as the so-called “multiple antigenic peptide” described in (Posneft, D.
- an immunogenic carrier such as serum albumin, tetanus toxoid, keyhole limpet hemocyanin, dextran, or a recombinant virus particle
- Spacers and linkers are typically comprised of relatively small, neutral molecules, such as amino acids and which are substantially uncharged under physiological conditions. Such spacers are typically selected from the group of nonpolar or neutral polar amino acids, such as glycine, alanine, serine and other similar amino acids. Such optional spacers or linkers need not be comprised of the same residues and thus may be either homo- or hetero-oligomers.
- linkers When present, such linkers will commonly be of length at least one or two, commonly 3, 4, 5, 6, and possibly as much as 10 or even up to 20 residues (in the case of amino acids). In addition, such linkers need not be composed of amino acids but any oligomeric structures will do as well so long as they provide the correct spacing so as to optimize the desired level of immunogenic activity of the immunogens of the present invention.
- the immunogen may therefore take any form that is capable of eliciting a CTL response.
- immunogenic peptides of the present invention may be part of an immunogenic structure via attachments other than conventional peptide bonds.
- any manner of attaching the peptides of the invention to an immunogen of the invention could provide an immunogenic structure as claimed herein.
- immunogens, such as proteins of the invention are structures that contain the peptides disclosed according to the present invention but such immunogenic peptides may not necessarily be attached thereto by the conventional means of using ordinary peptide bounds.
- the immunogens of the present invention simply contain such peptides as part of their makeup, but how such peptides are to be combined to form the final immunogen is left to the talent and imagination of the user and is in no way restricted or limited by the disclosure contained herein.
- the peptides may be modified at amino acid residues that are predicted to interact with the class I MHC molecule, in which case the goal is to create a peptide that has a higher affinity for the class I MHC molecule than does the original peptide.
- the peptides can also be modified at amino acid residues that are predicted to interact with the T cell receptor on the CTL, in which case the goal is to create a peptide that has a higher affinity for the T cell receptor than does the original peptide. Both of these types of modifications can result in a variant peptide that is related to an original peptide, but which is better able to induce a CTL response than is the original peptide.
- the term “original peptide” means an oligopeptide with the amino acid sequence selected from SEQ ID NO: 1-791 and 1514-1533.
- the original peptides disclosed herein can be modified by the substitution of one or more residues at different, possibly selective, sites within the peptide chain.
- substitutions may be of a conservative nature, for example, where one amino acid is replaced by an amino acid of similar structure and characteristics, such as where a hydrophobic amino acid is replaced by another hydrophobic amino acid. Even more conservative would be replacement of amino acids of the same or similar size and chemical nature, such as where leucine is replaced by isoleucine.
- Conservative substitutions are herein defined as exchanges within one of the following five groups: Group 1—small aliphatic, nonpolar or slightly polar residues (Ala, Ser, Thr, Pro, Gly); Group 2—polar, negatively charged residues and their amides (Asp, Asn, Glu, Gln); Group 3—polar, positively charged residues (His, Arg, Lys); Group 4—large, aliphatic, nonpolar residues (Met, Leu, lie, Val, Cys); and Group 4—large, aromatic residues (Phe, Tyr, Trp).
- substitutions may involve structures other than the common L-amino acids.
- D-amino acids might be substituted for the L-amino acids commonly found in the antigenic peptides of the invention and yet still be encompassed by the disclosure herein.
- amino acids possessing non-standard R groups i.e., R groups other than those found in the common 20 amino acids of natural proteins may also be used for substitution purposes to produce immunogens and immunogenic polypeptides according to the present invention.
- substitutions at more than one position are found to result in a peptide with substantially equivalent or greater antigenic activity as defined below, then combinations of those substitutions will be tested to determine if the combined substitutions result in additive or syngeneic effects on the antigenicity of the peptide. At most, no more than 4 positions within the peptide would simultaneously be substituted.
- an epitope is considered substantially identical to the reference peptide if it has at least 10% of the antigenic activity of the reference peptide as defined by the ability of the substituted peptide to reconstitute the epitope recognized by a CTL in comparison to the reference peptide.
- the observed percent specific killing of the target cells incubated with the substituted peptide should be equal to that of the reference peptide at an effector:target ratio that is no greater than 10-fold above the reference peptide effector:target ratio at which the comparison is being made.
- the peptide concentration at which the substituted peptides achieve half the maximal increase in lysis relative to background is no more than about 1 mM, preferably no more than about 1 ⁇ M, more preferably no more than about 1 nM, and still more preferably no more than about 100 ⁇ M, and most preferably no more than about 10 ⁇ M. It is also preferred that the substituted peptide be recognized by CTLs from more than one individual, at least two, and more preferably three individuals.
- the epitopes of the present invention may be identical to naturally occurring tumor-associated or tumor-specific epitopes or may include epitopes that differ by no more than 4 residues from the reference peptide, as long as they have substantially identical antigenic activity.
- an immunogen may consist only of a peptide of SEQ ID NO:1-791 or 1514-1533, or comprise a peptide of SEQ ID NO:1-791 or 1514-1533, or comprise a plurality of peptides selected from SEQ ID NO:1-791 and 1514-1533, or comprise a polypeptide that itself comprises one or more of the epitopic peptides of SEQ ID NO: 1-791 and 1514-1533.
- immunogenic peptides and polypeptides of the invention can be prepared synthetically, by recombinant DNA technology, or they can be isolated from natural sources such as tumor cells expressing the original protein product.
- polypeptides and oligopeptides disclosed herein can be synthesized in solution or on a solid support in accordance with conventional techniques.
- Various automated peptide synthesizers are commercially available and can be used in accordance with known protocols. See, for example, (Grant, G. A., Synthetic Peptides: A User's Guide, 1992, W. H. Freeman and Company, New York; Coligan, J. E. et al, Current Protocols in Protein Science, 1999, John Wiley & Sons, Inc., New York). Fragments of polypeptides of the invention can also be synthesized as intermediates in the synthesis of a larger polypeptide.
- Recombinant DNA technology may be employed wherein a nucleotide sequence which encodes an immunogenic peptide or polypeptide of interest is inserted into an expression vector, transformed or transfected into an appropriate host cell, and cultivated under conditions suitable for expression.
- These procedures are well known in the art to the skilled artisan, as described in (Coligan, J. E. et al, Current Protocols in Immunology, 1999, John Wiley & Sons, Inc., New York; Ausubel, F. M. et al, Current Protocols in Molecular Biology, 1999, John Wiley & Sons, Inc., New York; Molecular Cloning: A Laboratory Manual, 1989, Cold Spring Harbor Laboratory Press, Cold Spring Harbor).
- recombinantly produced peptides or polypeptides can be used as the immunogens of the invention.
- the coding sequences for peptides of the length contemplated herein can be synthesized on commercially available automated DNA synthesizers using protocols that are well know in the art. See for example, (Grant, G. A., Synthetic Peptides: A User's Guide, 1992, W. H. Freeman and Company, New York; Coligan, J. E. et al, Current Protocols in Protein Science, 1999, John Wiley & Sons, Inc., New York).
- the coding sequences can also be modified such that a peptide or polypeptide will be produced that incorporates a desired amino acid substitution.
- the coding sequence can be provided with appropriate linkers, be ligated into suitable expression vectors that are commonly available in the art, and the resulting DNA or RNA molecule can be transformed or transfected into suitable hosts to produce the desired fusion protein.
- suitable host systems are available, and their selection is left to the skilled artisan.
- the coding sequence will be provided with operably linked start and stop codons, promoter and terminator regions, and a replication system to provide an expression vector for expression in the desired host cell.
- promoter sequences compatible with bacterial hosts are provided in plasmids containing convenient restriction sites for insertion of the desired coding sequence.
- the resulting expression vectors are transformed into suitable bacterial hosts.
- yeast, insect, and mammalian host cells may also be used, employing suitable vectors and control sequences.
- Host cells are genetically engineered (transduced or transformed or transfected) with the vectors of this invention which may be, for example, a cloning vector or an expression vector.
- the vector may be, for example, in the form of a plasmid, a viral particle, a phage, etc.
- the engineered host cells can be cultured in conventional nutrient media modified as appropriate for activating promoters, selecting transformants or amplifying the genes of the present invention.
- the culture conditions such as temperature, pH and the like, are those previously used with the host cell selected for expression, and will be apparent to the ordinarily skilled artisan.
- the present invention also includes recombinant constructs comprising one or more of the sequences as broadly described above.
- the constructs comprise a vector, such as a plasmid or viral vector, into which a sequence of the invention has been inserted, in a forward or reverse orientation.
- the construct further comprises regulatory sequences, including, for example, a promoter, operably linked to the sequence.
- a promoter operably linked to the sequence.
- the present invention relates to host cells containing the above-described constructs.
- the host cell can be a higher eukaryotic cell, such as a mammalian cell, or a lower eukaryotic cell, such as a yeast cell, or the host cell can be a prokaryotic cell, such as a bacterial cell.
- Introduction of the construct into the host cell can be effected by calcium phosphate transfection, DEAE-Dextran mediated transfection, or electroporation (Ausubel, F. M. et al, Current Protocols in Molecular Biology, 1999, John Wiley & Sons, Inc., New York; Molecular Cloning: A Laboratory Manual, 1989, Cold Spring Harbor Laboratory Press, Cold Spring Harbor).
- Such cells can routinely be utilized for assaying CTL activity by having said genetically engineered, or recombinant, host cells express the immunogenic peptides of the present invention.
- mammalian cell culture systems can also be employed to express recombinant protein.
- mammalian expression systems include the COS-7 lines of monkey kidney fibroblasts, described by Gluzman, Cell, 23:175 (1981), and other cell lines capable of expressing a compatible vector, for example, the C127, 3T3, CHO, HeLa and BHK cell lines.
- Mammalian expression vectors will comprise an origin of replication, a suitable promoter and enhancer, and also any necessary ribosome binding sites, polyadenylation site, splice donor and acceptor sites, transcriptional termination sequences, and 5′ flanking non-transcribed sequences. DNA sequences derived from the SV40 splice, and polyadenylation sites may be used to provide the required nontranscribed genetic elements.
- the polypeptide can be recovered and purified from recombinant cell cultures by methods including ammonium sulfate or ethanol precipitation, acid extraction, anion or cation exchange chromatography, phosphocellulose chromatography, hydrophobic interaction chromatography, affinity chromatography, hydroxylapatite chromatography and lectin chromatography. Protein refolding steps can be used, as necessary, in completing configuration of the mature protein. High performance liquid chromatography (HPLC) can be employed for final purification steps.
- HPLC high performance liquid chromatography
- the immunogenic peptides of the present invention may be used to elicit CTLs ex vivo from either healthy individuals or from cancer patients with cancer, such as colorectal carcinoma, lung carcinoma, ovarian carcinoma, breast carcinoma, or prostate carcinoma. Such responses are induced by incubating in tissue culture the individual's CTL precursor lymphocytes together with a source of antigen presenting cells and the appropriate immunogenic peptide.
- suitable antigen presenting cells include dendritic cells, macrophages, and activated B cells.
- the peptide at concentrations between 10 and 40 ⁇ g/ml, would be pre-incubated with the antigen presenting cells for periods ranging from 1 to 18 hrs.
- ⁇ 2 -microglobulin (4 ⁇ g/ml) can be added during this time period to enhance binding.
- the antigen presenting cells may also be held at room temperature during the incubation period (Ljunggren, H.-G. et al., Nature, 346:476-480, (1990)) or pretreated with acid (Zeh, H. J., III et al., Hum. Immunol., 39:79-86, (1994)) to promote the generation of denatured class I MHC molecules which can then bind the peptide.
- the precursor CTLs are then added to the antigen presenting cells to which the immunogenic peptide has bound (stimulators) at responder to stimulator ratios of between 5:1 and 50:1, and most typically between 10:1 and 20:1.
- the co-cultivation of the cells is carried out at 37° C. in RPMI 1640, 10% fetal bovine serum, 2 mM L-glutamine, and IL-2 (5-20 Units/ml).
- Other cytokines such as IL-1, IL-7, and IL-12 may also be added to the culture.
- Fresh IL-2-containing media is added to the cultures every 2-4 days, typically by removing one-half the old media and replenishing it with an equal volume of fresh media.
- the CTL are re-stimulated with antigen presenting cells to which immunogenic peptide has been bound as described above.
- Fresh IL-2-containing media is added to the cells throughout their culture as described above. Three to four rounds of stimulation, and sometimes as many five to eight rounds of stimulation, are required to generate a CTL response that can then be measured in vitro.
- the above described protocol is illustrative only and should not be considered limiting. Many in vitro CTL stimulation protocols have been described and the choice of which one to use is well within the knowledge of the skilled artisan.
- the peptide-specific CTL can be further expanded to large numbers by treatment with anti-CD3 antibody. For example, see (Riddell, S. R. and Greenberg, P. D., J. Immunol. Methods, 128:189-201, (1990); Walter, E. A. et al., N. Engl. J. Med., 333:1038-1044, (1995)).
- Antigen presenting cells that are to be used to stimulate a CTL response are typically incubated with peptide of an optimal length, most commonly a nonapeptide, that allows for direct binding of the peptide to the class I MHC molecule without additional processing. Larger oligopeptides and polypeptides are generally ineffective in binding to class I MHC molecules as they are not efficiently processed into an appropriately sized peptide in the extracellular milieu. There a variety of approaches that are known in the art, however, that allow oligopeptides and polypeptides to be exogenously acquired by a cell, which then allows for their subsequent processing and presentation by a class I MHC molecule.
- Such approaches include electroporation of the molecules into the cell (Harding, C. H. III, Eur. J. Immunol., 22:1865-1869, (1992)), encapsulation of the molecules in liposomes which are fused to the cells of interest (Reddy, R. et al., J. Immunol. Methods, 141:157-163, (1991)), or osmotic shock in which the molecules are taken up via pinocytosis (Moore, M. W. et al., Cell, 54:777-785, (1988)).
- oligopeptides and polypeptides that comprise one or more of the peptides of the invention can be provided to antigen presenting cells in such a fashion that they are delivered to the cytoplasm of the cell, and are subsequently processed to allow presentation of the peptides.
- Antigen presenting cells suitable for stimulating an in vitro CTL response that is specific for one or more of the peptides of the invention can also be prepared by introducing polynucleotide vectors encoding the sequences into the cells.
- These polynucleotides can be designed such that they express only a single peptide of the invention, multiple peptides of the invention, or even a plurality of peptides of the invention.
- Such approaches include the introduction of plasmid DNA through particle-mediated gene transfer or electroporation (Tuting, T. et al., J. Immunol., 160:1139-1147, (1998)), or the transduction of cells with an adenovirus expressing the polynucleotide of interest (Perez-Diez, A. et al., Cancer Res., 58:5305-5309, (1998)).
- oligonucleotides that code for one or more of the peptides of the invention can be provided to antigen presenting cells in such a fashion that the peptides associate with class I MHC molecules and are presented on the surface of the antigen presenting cell, and consequently are available to stimulate a CTL response.
- stimulator cells By preparing the stimulator cells used to generate an in vitro CTL response in different ways, it is possible to control the peptide specificity of CTL response. For example, the CTLs generated with a particular peptide will necessarily be specific for that peptide Likewise, CTLs that are generated with a polypeptide or polynucleotide expressing or coding for particular peptides will be limited to specificities that recognize those peptides. More broadly, stimulator cells, and more specifically dendritic cells, can be incubated in the presence of the whole protein. As a further alternative, stimulator cells, and more specifically dendritic cells, can be transduced or transfected with RNA or DNA comprising the polynucleotide sequence encoding the protein.
- peptide epitopes that are naturally cleaved out of the protein, and which are generated in addition to peptide epitopes of SEQ ID NO:1-791 and 1514-1533 can associate with an appropriate class I MHC molecule, which may or may not include HLA-A1, -A2, or -A3.
- an appropriate class I MHC molecule which may or may not include HLA-A1, -A2, or -A3.
- the methods of the present invention include a method for inducing a CTL response in vitro that is specific for a tumor cell expressing a molecule from A1, A2, or A3 supertypes (A11 is a member of the A3 supertype), whereby the method comprises contacting a CTL precursor lymphocyte with an antigen presenting cell that has bound an immunogen comprising one or more of the peptides disclosed according to the invention.
- the methods of the present invention include a method for inducing a CTL response in vitro that is specific for a tumor cell expressing a molecule from A1, A2, or A3 supertypes, whereby the method comprises contacting a CTL precursor lymphocyte with an antigen presenting cell that has exogenously acquired an immunogenic oligopeptide or polypeptide that comprises one or more of the peptides disclosed according to the invention.
- a yet additional embodiment of the present invention is directed to a process for inducing a CTL response in vitro that is specific for a tumor cell expressing a molecule from A1, A2, or A3 supertypes, comprising contacting a CTL precursor lymphocyte with an antigen presenting cell that is expressing a polynucleotide coding for a polypeptide of the invention and wherein said polynucleotide is operably linked to a promoter.
- the methods of the present invention include a method for inducing a CTL response in vitro that is specific for a tumor cell expressing HLA-A1, HLA-A2, or HLA-A11, whereby the method comprises contacting a CTL precursor lymphocyte with an antigen presenting cell that has bound an immunogen comprising one or more of the peptides disclosed according to the invention.
- the methods of the present invention include a method for inducing a CTL response in vitro that is specific for a tumor cell expressing HLA-A1, HLA-A2, or HLA-A11, whereby the method comprises contacting a CTL precursor lymphocyte with an antigen presenting cell that has exogenously acquired an immunogenic oligopeptide or polypeptide that comprises one or more of the peptides disclosed according to the invention.
- a yet additional embodiment of the present invention is directed to a process for inducing a CTL response in vitro that is specific for a tumor cell expressing HLA-A1, HLA-A2, or HLA-A11, comprising contacting a CTL precursor lymphocyte with an antigen presenting cell that is expressing a polynucleotide coding for a polypeptide of the invention and wherein said polynucleotide is operably linked to a promoter.
- CTL A variety of techniques exist for assaying the activity of CTL. These techniques include the labeling of target cells with radionuclides such as Na 2 51 Cr0 4 or 3 H-thymidine, and measuring the release or retention of the radionuclides from the target cells as an index of cell death. Such assays are well-known in the art and their selection is left to the skilled artisan.
- CTL are known to release a variety of cytokines when they are stimulated by an appropriate target cell, such as a tumor cell expressing the relevant class I MHC molecule and the corresponding peptide.
- cytokines include IFN- ⁇ , TNF ⁇ , and GM-CSF.
- the antigen-specific CTLs After expansion of the antigen-specific CTLs, the latter are then adoptively transferred back into the patient, where they will destroy their specific target cell.
- the utility of such adoptive transfer is demonstrated in North, R. J. et al. (Infect. Immun., 67:2010-2012, (1999)) and Riddell, S. R. et al. (Science, 257:238-241, (1992)).
- the skilled physician will be guided by the total number of cells available, the activity of the CTL as measured in vitro, and the condition of the patient.
- about 1 ⁇ 10 6 to about 1 ⁇ 10 12 , more preferably about 1 ⁇ 10 8 to about 1 ⁇ 10 11 , and even more preferably, about 1 ⁇ 10 9 to about 1 ⁇ 10 10 peptide-specific CTL are infused.
- Methodology for reinfusing the T cells into a patient are well known and exemplified in U.S. Pat. No. 4,844,893 to Honski, et al., and U.S. Pat. No. 4,690,915 to Rosenberg.
- the peptide-specific CTL can be purified from the stimulator cells prior to infusion into the patient.
- monoclonal antibodies directed towards the cell surface protein CD8, present on CTL can be used in conjunction with a variety of isolation techniques such as antibody panning, flow cytometric sorting, and magnetic bead separation to purify the peptide-specific CTL away from any remaining non-peptide specific lymphocytes or from the stimulator cells. These methods are well known in the art, and are their selection is left to the skilled artisan. It should be appreciated that generation of peptide-specific CTL in this manner, obviates the need for stimulating the CTL in the presence of tumor. Thus, there is no chance of inadvertently reintroducing tumor cells into the patient.
- one embodiment of the present invention relates to a process for treating a subject with cancer characterized by tumor cells expressing complexes of a molecule from A1, A2, or A3 supertypes, for example, HLA-A1, HLA-A2, or HLA-A11, whereby CTLs produced in vitro according to the present invention are administered in an amount sufficient to destroy the tumor cells through direct lysis or to effect the destruction of the tumor cells indirectly through the elaboration of cytokines.
- Another embodiment of the present invention is directed to a process for treating a subject with cancer characterized by tumor cells expressing any class I MHC molecule and an epitope of SEQ ID NO: 1-791 and 1514-1533, whereby the CTLs are produced in vitro and are specific for the epitope or original protein and are administered in an amount sufficient to destroy the tumor cells through direct lysis or to effect the destruction of the tumor cells indirectly through the elaboration of cytokines.
- the cancer to be treated may include a colorectal carcinoma, an ovarian carcinoma, a breast carcinoma, a lung carcinoma, and prostate carcinoma, but especially ovarian carcinoma.
- the ex vivo generated CTL can be used to identify and isolate the T cell receptor molecules specific for the peptide.
- the genes encoding the alpha and beta chains of the T cell receptor can be cloned into an expression vector system and transferred and expressed in naive T cells from peripheral blood, T cells from lymph nodes, or T lymphocyte progenitor cells from bone marrow. These T cells, which would then be expressing a peptide-specific T cell receptor, would then have anti-tumor reactivity and could be used in adoptive therapy of cancer, and more specifically cancer, colorectal carcinoma, ovarian carcinoma, breast carcinoma, lung carcinoma, and prostate carcinoma.
- the immunogenic peptides of the present invention are useful as screening and diagnostic agents.
- the immunogenic peptides of the present invention together with modern techniques of gene screening, make it possible to screen patients for the presence of genes encoding such peptides on cells obtained by biopsy of tumors detected in such patients. The results of such screening may help determine the efficacy of proceeding with the regimen of treatment disclosed herein using the immunogens of the present invention.
- the immunogenic peptides disclosed herein, as well as functionally similar homologs thereof, may be used to screen a sample for the presence of CTLs that specifically recognize the corresponding epitopes.
- the lymphocytes to be screened in this assay will normally be obtained from the peripheral blood, but lymphocytes can be obtained from other sources, including lymph nodes, spleen, tumors, and pleural fluid.
- the peptides of the present invention may then be used as a diagnostic tool to evaluate the efficacy of the immunotherapeutic treatments disclosed herein.
- the in vitro generation of CTL as described above would be used to determine if patients are likely to respond to the peptide in vivo.
- the in vitro generation of CTL could be done with samples of lymphocytes obtained from the patient before and after treatment with the peptides. Successful generation of CTL in vivo should then be recognized by a correspondingly easier ability to generate peptide-specific CTL in vitro from lymphocytes obtained following treatment in comparison to those obtained before treatment.
- the oligopeptides of the invention can also be used to prepare class I MHC tetramers which can be used in conjunction with flow cytometry to quantitate the frequency of peptide-specific CTL that are present in a sample of lymphocytes from an individual.
- class I MHC molecules comprising peptides of SEQ ID NO: 1-791 and 1514-1533, would be combined to form tetramers as exemplified in U.S. Pat. No. 5,635,363.
- Said tetramers would find use in monitoring the frequency of CTLs in the peripheral blood, lymph nodes, or tumor mass of an individual undergoing immunotherapy with the peptides, proteins, or polynucleotides of the invention, and it would be expected that successful immunization would lead to an increase in the frequency of the peptide-specific CTL.
- a vaccine in accordance with the present invention may include one or more of the hereinabove described polypeptides or active fragments thereof, or a composition, or pool, of immunogenic peptides disclosed herein.
- two or more polypeptides and/or active fragments may be used as a physical mixture or as a fusion of two or more polypeptides or active fragments.
- the fusion fragment or fusion polypeptide may be produced, for example, by recombinant techniques or by the use of appropriate linkers for fusing previously prepared polypeptides or active fragments.
- the immunogenic molecules of the invention may be utilized according to the present invention for purposes of preventing, suppressing or treating diseases causing the expression of the immunogenic peptides disclosed herein, such as where the antigen is being expressed by tumor cells.
- prevention relates to a process of prophylaxis in which an animal, especially a mammal, and most especially a human, is exposed to an immunogen of the present invention prior to the induction or onset of the disease process. This could be done where an individual has a genetic pedigree indicating a predisposition toward occurrence of the disease condition to be prevented.
- the immunogen could be administered to the general population as is frequently done for infectious diseases.
- the term “suppression” is often used to describe a condition wherein the disease process has already begun but obvious symptoms of said condition have yet to be realized.
- the cells of an individual may have become cancerous but no outside signs of the disease have yet been clinically recognized.
- the term prophylaxis can be applied to encompass both prevention and suppression.
- the term “treatment” is often utilized to mean the clinical application of agents to combat an already existing condition whose clinical presentation has already been realized in a patient. This would occur where an individual has already been diagnosed as having a tumor.
- the suitable dosage of an immunogen of the present invention will depend upon the age, sex, health, and weight of the recipient, the kind of concurrent treatment, if any, the frequency of treatment, and the nature of the effect desired. However, the most preferred dosage can be tailored to the individual subject, as determined by the researcher or clinician.
- the total dose required for any given treatment will commonly be determined with respect to a standard reference dose as set by a manufacturer, such as is commonly done with vaccines, such dose being administered either in a single treatment or in a series of doses, the success of which will depend on the production of a desired immunological result (i.e., successful production of a CTL-mediated response to the antigen, which response gives rise to the prevention and/or treatment desired).
- the overall administration schedule must be considered in determining the success of a course of treatment and not whether a single dose, given in isolation, would or would not produce the desired immunologically therapeutic result or effect.
- the therapeutically effective amount of a composition containing one or more of the immunogens of this invention is an amount sufficient to induce an effective CTL response to the antigen and to cure or arrest disease progression.
- this dose will depend, among other things, on the identity of the immunogens used, the nature of the disease condition, the severity of the disease condition, the extent of any need to prevent such a condition where it has not already been detected, the manner of administration dictated by the situation requiring such administration, the weight and state of health of the individual receiving such administration, and the sound judgment of the clinician or researcher.
- effective amounts would generally lie within the range of from 1.0 ⁇ g to about 5,000 ⁇ g of peptide for a 70 kg patient, followed by boosting dosages of from about 1.0 ⁇ g to about 1,000 ⁇ g of peptide pursuant to a boosting regimen over days, weeks or even months, depending on the recipient's response and as necessitated by subsequent monitoring of CTL-mediated activity within the bloodstream.
- dosages are to be considered only a general guide and, in a given situation, may greatly exceed such suggested dosage regimens where the clinician believes that the recipient's condition warrants more a aggressive administration schedule.
- the efficacy of administering additional doses, and of increasing or decreasing the interval may be re-evaluated on a continuing basis, in view of the recipient's immunocompetence (for example, the level of CTL activity with respect to tumor-associated or tumor-specific antigens).
- the immunogenic compositions according to the present invention may be used against a disease condition such as cancer by administration to an individual by a variety of routes.
- the composition may be administered parenterally or orally, and, if parenterally, either systemically or topically.
- Parenteral routes include subcutaneous, intravenous, intradermal, intramuscular, intraperitoneal, intranasal, transdermal, or buccal routes. One or more such routes may be employed.
- Parenteral administration can be, for example, by bolus injection or by gradual perfusion over time.
- vaccines are prepared as injectables, in the form of aqueous solutions or suspensions. Vaccines in an oil base are also well known such as for inhaling. Solid forms which are dissolved or suspended prior to use may also be formulated. Pharmaceutical carriers, diluents and excipients are generally added that are compatible with the active ingredients and acceptable for pharmaceutical use.
- Such carriers include, but are not limited to, water, saline solutions, dextrose, or glycerol. Combinations of carriers may also be used. These compositions may be sterilized by conventional, well known sterilization techniques including sterile filtration. The resulting solutions may be packaged for use as is, or the aqueous solutions may be lyophilized, the lyophilized preparation being combined with sterile water before administration. Vaccine compositions may further incorporate additional substances to stabilize pH, or to function as adjuvants, wetting agents, or emulsifying agents, which can serve to improve the effectiveness of the vaccine.
- the concentration of the CTL stimulatory peptides of the invention in pharmaceutical formulations are subject to wide variation, including anywhere from less than 0.01% by weight to as much as 50% or more. Factors such as volume and viscosity of the resulting composition must also be considered.
- the solvents, or diluents, used for such compositions include water, possibly PBS (phosphate buffered saline), or saline itself, or other possible carriers or excipients.
- the immunogens of the present invention may also be contained in artificially created structures such as liposomes, ISCOMS, slow-releasing particles, and other vehicles which increase the immunogenicity and/or half-life of the peptides or polypeptides in serum.
- Liposomes include emulsions, foams, micelies, insoluble monolayers, liquid crystals, phospholipid dispersions, lamellar layers and the like.
- Liposomes for use in the invention are formed from standard vesicle-forming lipids which generally include neutral and negatively charged phospholipids and a sterol, such as cholesterol. The selection of lipids is generally determined by considerations such as liposome size and stability in the blood.
- Liposomes containing the peptides or polypeptides of the invention can be directed to the site of lymphoid cells where the liposomes then deliver the selected immunogens directly to antigen presenting cells.
- Targeting can be achieved by incorporating additional molecules such as proteins or polysaccharides into the outer membranes of said structures, thus resulting in the delivery of the structures to particular areas of the body, or to particular cells within a given organ or tissue.
- Such targeting molecules may a molecule that binds to receptor on antigen presenting cells.
- an antibody that binds to CD80 could be used to direct liposomes to dendritic cells.
- the immunogens of the present invention may also be administered as solid compositions.
- Conventional nontoxic solid carriers including pharmaceutical grades of mannitol, lactose, starch, magnesium, cellulose, glucose, sucrose, sodium saccharin, and the like.
- Such solid compositions will often be administered orally, whereby a pharmaceutically acceptable nontoxic composition is formed by incorporating the peptides and polypeptides of the invention with any of the carriers listed above.
- such compositions will contain 10-95% active ingredient, and more preferably 25-75% active ingredient.
- Aerosol administration is also an alternative, requiring only that the immunogens be properly dispersed within the aerosol propellant.
- Typical percentages of the peptides or polypeptides of the invention are 0.01%-20% by weight, preferably 1%-10%.
- the use of a surfactant to properly disperse the immunogen may be required.
- Representative surfactants include the esters or partial esters of fatty acids containing from 6 to 22 carbon atoms, such as caproic, octanoic, lauric, palmitic, stearic, linoleic, linolenic, olesteric and oleic acids with an aliphatic polyhydric alcohol or its cyclic anhydride.
- esters such as mixed or natural glycerides may be employed.
- the surfactant may constitute 0.1-20% by weight of the composition, preferably 0.25-5%.
- Typical propellants for such administration may include esters and similar chemicals but are by no means limited to these.
- a carrier, such as lecithin for intranasal delivery, may also be included.
- the peptides and polypeptides of the invention may also be delivered with an adjuvant.
- Adjuvants include, but are not limited to complete or incomplete Freund's adjuvant, Montanide ISA-51, Lymphocyte Activation Gene-3 (LAG-)3, aluminum phosphate, aluminum hydroxide, alum, and saponin.
- Adjuvant effects can also be obtained by injecting a variety of cytokines along with the immunogens of the invention. These cytokines include, but are not limited to IL-1, IL-2, IL-7, IL-12, and GM-CSF.
- the peptides and polypeptides of the invention can also be added to professional antigen presenting cells such as dendritic cells that have been prepared ex vivo.
- the dendritic cells could be prepared from CD34 positive stem cells from the bone marrow, or they could be prepared from CD14 positive monocytes obtained from the peripheral blood.
- the dendritic cells are generated ex vivo using cytokines such as GM-CSF, IL-3, IL-4, TNF, and SCF.
- the cultured DC are then pulsed with peptides at various concentrations using standard methods that are well known in the art.
- the peptide-pulsed dendritic cells can then be administered either intraveneously, subcutaneously, or intradermally, and the immunization may also include cytokines such as IL-2 or IL-12.
- the present invention is also directed to a vaccine in which an immunogen of the present invention is delivered or administered in the form of a polynucleotide encoding the a polypeptide or active fragment as disclosed herein, whereby the peptide or polypeptide or active fragment is produced in vivo.
- the polynucleotide may be included in a suitable expression vector and combined with a pharmaceutically acceptable carrier.
- the peptides or polypeptides could be expressed in plasmid DNA and nonreplicative viral vectors such as vaccinia, fowlpox, Venezuelan equine encephalitis virus, adenovirus, or other RNA or DNA viruses.
- compositions containing the immunogens disclosed herein may, in addition, contain other antitumor pharmaceuticals.
- the use of such compositions with multiple active ingredients is left to the discretion of the clinician.
- the immunogens of the present invention can be used to stimulate the production of antibodies for use in passive immunotherapy, for use as diagnostic reagents, and for use as reagents in other processes such as affinity chromatography.
- the present invention also relates to antibodies that react with immunogens, such as a polypeptide comprising one or more of the epitopic peptides of SEQ ID NO: 1-791 and 1514-1533 as disclosed herein. Active fragments of such antibodies are also specifically contemplated. Such antibodies, and active fragments of such antibodies, for example, and Fab structure, may react with, including where it is highly selective or specific for, an immunogenic structure comprising 2, 3, 4 or more of the epitopic peptides of the invention.
- immunogens such as a polypeptide comprising one or more of the epitopic peptides of SEQ ID NO: 1-791 and 1514-1533 as disclosed herein.
- Active fragments of such antibodies are also specifically contemplated.
- Such antibodies, and active fragments of such antibodies, for example, and Fab structure may react with, including where it is highly selective or specific for, an immunogenic structure comprising 2, 3, 4 or more of the epitopic peptides of the invention.
- Such antibodies can be produced by either cloning the gene sequences encoding the polypeptide chains of said antibodies or by direct synthesis of said polypeptide chains, with in vitro assembly of the synthesized chains to form active tetrameric (H 2 L 2 ) structures with affinity for specific epitopes and antigenic determinants. This has permitted the ready production of antibodies having sequences characteristic of neutralizing antibodies from different species and sources.
- H 2 L 2 refers to the fact that antibodies commonly comprise 2 light (L) amino acid chains and 2 heavy (H) amino acid chains. Both chains have regions capable of interacting with a structurally complementary antigenic target. The regions interacting with the target are referred to as “variable” or “V” regions and are characterized by differences in amino acid sequence from antibodies of different antigenic specificity.
- variable regions of either H or L chains contains the amino acid sequences capable of specifically binding to antigenic targets. Within these sequences are smaller sequences dubbed “hypervariable” because of their extreme variability between antibodies of differing specificity. Such hypervariable regions are also referred to as “complementarity determining regions” or “CDR” regions. These CDR regions account for the basic specificity of the antibody for a particular antigenic determinant structure.
- variable heavy and light chains of all antibodies each have 3 CDR regions, each non-contiguous with the others (termed L1, L2, L3, H1, H2, H3) for the respective light (L) and heavy (H) chains.
- L1, L2, L3, H1, H2, H3 The accepted CDR regions have been described in the text and figures of Kabat et al. (J. Biol. Chem. 252:6609-6616 (1977)).
- antibody polypeptides contain constant (i.e., highly conserved) and variable regions, and, within the latter, there are the CDRs and the so-called “framework regions” made up of amino acid sequences within the variable region of the heavy or light chain but outside the CDRs.
- the antibodies disclosed according to the invention may also be wholly synthetic, wherein the polypeptide chains of the antibodies are synthesized and, possibly, optimized for binding to the polypeptides disclosed herein as being receptors.
- Such antibodies may be chimeric or humanized antibodies and may be fully tetrameric in structure, or may be dimeric and comprise only a single heavy and a single light chain.
- Such antibodies may also include fragments, such as Fab and F(ab 2 )′ fragments, capable of reacting with and binding to any of the polypeptides disclosed herein as being receptors.
- a further embodiment of the present invention relates to a method for inducing a CTL response in a subject comprising administering to subjects that express HLA-A1 antigens an effective (i.e., CTL-stimulating amount) of an immunogen of the invention that does not comprise the entire protein expressing the epitopic peptides disclosed herein (i.e., one that comprises less than the entire protein where the protein is a naturally occurring polypeptide) in an amount sufficient to induce a CTL response to tumor cells expressing at least HLA-A1 or HLA-A2, as the case may be, thereby eliciting a cellular response against said tumor cells.
- an effective i.e., CTL-stimulating amount
- a still further embodiment of the present invention relates to a method for inducing a CTL response in a subject, wherein the immunogen is in the form of a polynucleotide.
- the method comprises administering to subjects that express HLA-A1 at least one CTL epitope, wherein said epitope or epitopes are selected from a group comprising the peptides disclosed according to the invention, and are coded within a polynucleotide sequence that does not comprise the entire protein coding region, in an amount sufficient to induce a CTL response to tumor cells expressing HLA-A1 or HLA-A2.
- ARGOV57 a HLA-A1/11 positive ovarian cell line, was established by culturing tumor cells from an ascitic fluid from an ovarian patient.
- OVCAR3 a HLA-A2 positive ovarian carcinoma cell line, was established by culturing tumor cells from an ascitic fluid from an ovarian patient.
- SKOV3-A2 a HLA-A2 stably expressing ovarian carcinoma cell line, was established by culturing tumor cells from an ascitic fluid from an ovarian patient and transduced with HLA-A2 gene.
- ARGOV57 cells were grown in 10-chamber Nunc cell factories (Fisher, Pittsburgh, Pa.). The cells were harvested by treatment with 0.45% trypsin and 0.32 mM EDTA, washed two times in phosphate-buffered saline solution (pH 7.4), and stored as cell pellets at ⁇ 80° C.
- the lysates were then centrifuged at 100,000 ⁇ g, the pellets discarded, and the supernatants passed through a 0.22 ⁇ m filter.
- the supernatants were then passed over a series of columns with the first containing Sepharose, and the second containing the HLA-A1-specific monoclonal antibody, GAP-A1, bound to a protein A-Sepharose matrix.
- the second column was then sequentially washed with 20 column volumes of 20 mM Tris, pH 8.0, 150 mM NaCl, 20 column volumes of 20 mM Tris, pH 8.0, 1.0 M NaCl, and 20 column volumes of 20 mM Tris, pH 8.0.
- the peptides were eluted from the column with 5 column volumes of 10% acetic acid.
- the isolated HLA-A1 molecules were then boiled for 5 min to further dissociate any bound peptide from the heavy chains.
- the peptides were then separated from the co-purifying class I heavy chain and ⁇ 2 -microglobulin by centrifugation on a Ultrafree-CL membrane with a nominal molecular weight cut-off of 5,000 Daltons (Millipore, Bedford, Mass.).
- OVCAR3 or SKOV3 cells were successfully prepared using the same procedure as just described except that HLA-A2 molecules were prepared using HLA-A2 specific antibodies.
- the peptide extracts were fractionated by RP-HPLC (Reversed Phase-High Performance Liquid Chromatography) using an Applied Biosystems (ABI) model 140B system.
- the extracts were concentrated by vacuum centrifugation from about 20 ml down to 250 ⁇ l and injected into either a Brownlee (Norwalk, Conn.) C 18 Aquapore column (2.1 mm ⁇ 3 cm; 300 ⁇ ; 7 ⁇ m) or a Higgins (Mountain View, Calif.) C18 Haisil column (2.1 mm ⁇ 4 cm; 300 ⁇ ; 5 ⁇ m).
- the peptides were eluted by first using a gradient of acetonitrile/0.085% TFA (trifluoroacetic acid) in 0.1% TFA/water, with the concentration of acetonitrile increasing from 0-9% (0-5 minutes), 9-36% (5-55 minutes), and 36-60% (55-62 minutes).
- a second dimension fractionation of combined fractions 17 and 18 from the first dimension (TFA) fraction was accomplished using the same gradient but with the substitution of HFBA (heptafluorobutyric acid) for TFA.
- the flow rate was 200 ⁇ l/min, and fractions were collected at 1 min (Brownlee column) or 40 second (Higgins column) intervals.
- a third dimension of RP-HPLC was achieved using an Eldex (Napa, Calif.) MicroPro Pump, a homemade C 18 microcapillary column, and an ABI model 785A UV absorbance detector.
- the column was prepared by packing a 27 cm bed of 10 ⁇ m C 18 particles in a section of 285 ⁇ m o.d./75 ⁇ m i.d. fused silica (Polymicro Technologies, Phoenix, Ariz.).
- Peptides in combined fractions 26 and 27 of the second dimension fraction were loaded onto this column and eluted with a gradient of acetonitrile/0.67% triethylamine acetate/water in 0.1% triethylamine acetate/water, with the concentration of acetonitrile increasing from 0-60% in 40 minutes.
- the flow rate was about 300 nl/min, and fractions were collected into 25 ⁇ l of water every 30 s.
- peptides were detected by monitoring UV absorbance at 214 nm.
- the second dimension HPLC fraction was analyzed using an affluent splitter on the microcapillary HPLC column.
- the column (360 ⁇ m o.d. X 100 ⁇ m i.d. with a 25 cm C 18 bed) was butt connected with a zero dead volume tee (Valco, Houston, Tex.) to two pieces of fused silica of different lengths (25 ⁇ m and 40 ⁇ m i.d.). Peptides were eluted with a 34 min gradient of 0-60% acetonitrile.
- Proteins containing peptides corresponding to the masses identified by MS were analyzed with the search algorithm, SEQUEST. Searches were also carried out on the GenBank non-redundant sequence database (http://ncbi.nlm.nih.-gov/Entrez/) as well as on our own unique database of 2943 specific sequences compiled from GenBank and EST data-base entries. Upon experimental confirmation of the peptide sequence, a tBLASTn search of the GenBank non-redundant database was performed to identify any genes containing the DNA sequence encoding the peptide.
- Peptides were synthesized using a Gilson (Madison, Wis.) AMS 422 multiple peptide synthesizer. Quantities of 10 ⁇ Mol were synthesized using conventional FMOC amino acids, resins, and chemical techniques. Peptides were purified by RP-HPLC using a 4.6 mm ⁇ 100 mm POROS (Perseptive Biosystems, Cambridge, Mass.) column and a 10 min, 0-60% acetonitrile in 0.1% TFA gradient.
- PBMC peripheral blood mononuclear cells
- Adherent PBMC ( ⁇ 8.3 ⁇ 10 5 /well) were then pulsed with 50 mg/ml synthetic peptides in serum-free AIM-V medium containing 1.5 mg/ml ⁇ 2 -microg lobulin (Calbiochem-Novabiochem, San Diego, Calif.) and incubated for 2 h at 37° C. Unbound peptides were aspirated and the wells washed with media.
- Monocyte-derived DC were generated as follows. PBMC (5.3 ⁇ 10 7 ) were allowed to adhere in T-75 flasks (Corning) in 10 ml of serum-free AIM-V medium for 60 min at 37° C. Non-adherent cells were collected as a source of effector T cells and pooled with the previous collection above. Adherent monocytes in flasks were then exposed to recombinant human granulocyte macrophage colony stimulating factor (GM-CSF, 25 ng/ml; Peprotech) and recombinant human IL-4 (100 ng/ml; Peprotech) in 10 ml of AIM-V medium containing 10% heat-inactivated FBS.
- DC obtained by this method [immature DC (iDC)] are characterized by expression of low levels of CD83, CD80, CD86, and HLA class I and class II molecules (data not shown).
- Mature DC were obtained by exposing day 5 DC cultures to recombinant soluble CD40 ligand (sCD40L; Peprotech) at 1.5 mg/ml for 24 h in the presence of 25 ng/ml GM-CSF and are characterized by expression of high levels of CD80, CD86, and HLA class I and class II molecules.
- mDC were harvested, washed, pulsed with 5 mg/ml peptide in serum-free AIM-V medium and irradiated (5000 rad) prior to use as stimulators.
- the protocol used here is a modification of the method described by Plebanski et al. (Eur. J. Immunol. 25:1783, (1995)).
- CTL to peptide were generated by 3 ⁇ 4 cycles of stimulation with peptide-loaded APC.
- T cells or non-adherent PBMC from above were added in bulk (CD4 + , CD8 + , NK, etc.) to adherent PBMC-loaded peptides in serum-free medium (50 mg/ml), ⁇ 2 -microglobulin (1.5 mg/ml) (Calbiochem-Novabiochem), recombinant human IL-7 (5 ng/ml) (Peprotech) and keyhole limpet hemocyanin (5 mg/ml) (Sigma, St Louis, Mo.).
- T cells were transferred to new plates by first aspirating 70% of spent media in wells and then transferring the pooled contents to a new plate. Fresh IL-7 was added at each re-stimulation.
- the responder:stimulator (T cell:DC) ratio was set at 20 for each stimulation.
- Recombinant human IL-2 (10 U/ml) was added on day 5 after each re-stimulation.
- the T cells Prior to 51 Cr-release assay, the T cells were harvested and CD8 + T cells were purified by positive selection using CD8 + microbeads immunomagnetic cell separation with MACS kit (Miltenyi Biotec, Auburn, Calif.). If a fourth round of stimulation was necessary following CTL analysis, the CTL were pulsed as before, except with 5 ⁇ 10 mg/ml of peptide.
- HLA-A2-allospecific CTL were obtained in a mixed lymphocyte reaction by repeated stimulation of HLA-A3 + PBMC (responders) with irradiated HLA-A2 + stimulator PBMC at a ratio of 10:1 in the presence of 10 U/ml IL-2. Stimulation was repeated weekly with PBMC from different HLA-A2 + donors so as to minimize alloresponse to non-HLA-A2 antigens. T cells were assessed for lysis on several HLA-A2 + targets including tumor cells, EBV-B cells and HLA-A3 + targets every week after the third round of stimulation.
- Expansion of large numbers of peptide-specific or HLA-A2-allospecific CTL was achieved by culturing 5.3 ⁇ 10 4 ⁇ 1.3 ⁇ 10 5 T cells around day 6 or 7 post peptide- or allostimulation in the presence of 2.5-3.0 ⁇ 10 7 irradiated (5000 rad) allogeneic normal donor PBMC coated with anti-CD3 antibody at 10 ng/ml (BD PharMingen, San Diego, Calif.) and 25 U/ml of recombinant human IL-2 (Peprotech) in a final volume of 30 ml RPMI medium. Media changes with IL-2 addition (50 U/ml) were effected on days 5 and 8. Cells were harvested for cytotoxicity assays on days 10 ⁇ 12 and re-stimulated or frozen for later use.
- Target cells in suspension T2, C1R.A2, B-LCL and K562
- 100 mCi Na 2 51 CrO4 NEN Life Science, Boston, Mass.
- 5 ml RPMI 1640 media containing 2 ⁇ 5% FBS or for 60 ⁇ 90 min at 37° C. directly with the cell pellet in the case of adherent cells (tumor cell lines and control lines).
- Labeling was terminated by washing the targets with cold media containing 5% FBS for a total of three washes.
- Target cells were resuspended at a concentration of 2 ⁇ 3 ⁇ 10 4 /ml. About 2 ⁇ 3 ⁇ 10 3 targets in 100 ml were delivered to each well containing CTL (effectors) seeded at different E:T ratios. Spontaneous release wells contained targets in media alone, while maximal release wells contained targets in 2% NP-40 detergent (Igepal CA-630; Sigma). HLA restriction of CTL-mediated killing was achieved by preincubation of targets with HLA-specific antibodies prior to incubation with CTL.
- Peptide-stimulated CTL were reacted with 51 Cr-labeled Ov2 tumor cells (E:T ratio of 40) in the presence of excess of cold targets in a 4-h Cr-release assay.
- Cold targets were either empty T2 cells, T2 cells pulsed with 1 mg/ml relevant peptide (used to stimulate CTL) or irrelevant (control) peptides (HER-2/neu 369 ⁇ 377 or MART 127 ⁇ 35), or IFN- ⁇ pre-treated tumor cells (SKOV3.A2 and OVCAR 3) with the cold target in 5-fold excess of the hot target.
- Results indicate that (i) CTL show specific interaction with the peptide to which they are sensitized to, and (ii) CTL compete for similar epitopes presented on Ov2 as were found in SKOV3.A2 and OVCAR3 cell lines by MS.
Abstract
The present invention relates to compositions and methods for the prevention, treatment, and diagnosis of cancer, especially carcinomas, such as ovarian carcinoma. The invention discloses peptides, polypeptides, and polynucleotides that can be used to stimulate a CTL response against cancer.
Description
- This application is a continuation of U.S. application Ser. No. 11/426,161, filed Jun. 23, 2006, which is a continuation-in-part of U.S. application Ser. No. 10/006,177, filed Dec. 4, 2001, now U.S. Pat. No. 7,083,789, which claims priority from U.S. provisional application No. 60/251,022, filed Dec. 4, 2000, and U.S. provisional application No. 60/256,824, filed Dec. 20, 2000, the disclosures of which are all herein incorporated by reference in their entireties.
- The Sequence Listing has been submitted electronically as file 09191—0002U5_sequence_listing.txt, 5.96 MB, created Feb. 17, 2011 and is hereby incorporated by reference.
- The present invention relates generally to the field of immunogens whose structures incorporate polypeptides comprising epitopic peptides derived from proteins expressed by cancer cells and to uses of said immunogens in eliciting cytotoxic T lymphocyte (CTL) responses for the diagnosis, prevention and treatment of cancer, preferably carcinoma, most preferably ovarian carcinoma.
- The mammalian immune system has evolved a variety of mechanisms to protect the host from cancerous cells, an important component of this response being mediated by cells referred to as T cells. Cytotoxic T lymphocytes (CTLs) are specialized T cells that function primarily by recognizing and killing cancerous cells or infected cells, but also by secreting soluble molecules referred to as cytokines that can mediate a variety of effects on the immune system.
- Evidence suggests that immunotherapy designed to stimulate a tumor-specific CTL response would be effective in controlling cancer. For example, it has been shown that human CTLs recognize sarcomas (Slovin, S. F. et al., J. Immunol., 137:3042-3048, (1987)), renal cell carcinomas (Schendel, D. J. et al., J. Immunol., 151:4209-4220, (1993)), colorectal carcinomas (Jacob, L. et al., Int. J. Cancer, 71:325-332, (1997)), ovarian carcinomas (Loannides, C. G. et al., J. Immunol., 146:1700-1707, (1991)) (Peoples, G. E. et al., Surgery, 114:227-234, (1993)), pancreatic carcinomas (Peiper, M. et al., Eur. J. Immunol., 27:1115-1123, (1997); Wolfel, T. et al., Int. J. Cancer, 54:636-644, (1993)), squamous tumors of the head and neck (Yasumura, S. et al., Cancer Res., 53:1461-1468, (1993)), and squamous carcinomas of the lung (Slingluff, C. L. Jr et al., Cancer Res., 54:2731-2737, (1994); Yoshino, I. et al., Cancer Res., 54:3387-3390, (1994)). The largest number of reports of human tumor-reactive CTLs have concerned cancers (Boon, T. et al., Ann. Rev. Immunol., 12:337-365, (1994)). The ability of tumor-specific CTLs to mediate tumor regression, in both human (Rosenberg, S. A. et al., N. Engl. J. Med., 319:1676-1680, (1988)) and animal models (Celluzzi, C. M. et al., J. Exp. Med., 183:283-287, (1996); Mayordomo, J. I. et al., Nat. Med., 1:1297-1302, (1995); Zitvogel, L. et al., J. Exp. Med., 183:87-97, (1996)), suggests that methods directed at increasing CTL activity would likely have a beneficial effect with respect to tumor treatment.
- In order for CTLs to kill or secrete cytokines in response to a cancer cell, the CTL must first recognize that cell as being cancerous. This process involves the interaction of the T cell receptor, located on the surface of the CTL, with what is generically referred to as an MHC-peptide complex which is located on the surface of the cancerous cell. MHC (major histocompatibility-complex)-encoded molecules have been subdivided into two types, and are referred to as class I and class II MHC-encoded molecules.
- In the human immune system, MHC molecules are referred to as human leukocyte antigens (HLA). Within the MHC, located on chromosome six, are three different genetic loci that encode for class I MHC molecules. MHC molecules encoded at these loci are referred to as HLA-A, HLA-B, and HLA-C. The genes that can be encoded at each of these loci are extremely polymorphic, and thus, different individuals within the population express different class I MHC molecules on the surface of their cells. HLA-A1, HLA-A2, HLA-A3, HLA-B7, and HLA-B8 are examples of different class I MHC molecules that can be expressed from these loci. The present disclosure involves peptides that are associated with the HLA-A1, HLA-A2, or HLA-A11 molecules, HLA-A1 supertypes, HLA-A2 supertypes, and HLA-A11 supertypes and with the gene and protein that gives rise to these peptides. A supertype is a group of HLA molecules that present at least one shared epitope.
- The peptides that associate with the MHC molecules can either be derived from proteins made within the cell, in which case they typically associate with class I MHC molecules (Rock, K. L. and Golde, U., Ann. Rev. Immunol., 17:739-779, (1999)) or they can be derived from proteins that are acquired from outside of the cell, in which case they typically associate with class II MHC molecules (Watts, C., Ann. Rev. Immunol., 15:821-850, (1997)). Peptides that evoke a cancer-specific CTL response most typically associate with class I MHC molecules. The peptides that associate with a class I MHC molecule are typically nine amino acids in length, but can vary from a minimum length of eight amino acids to a maximum of fourteen amino acids in length. A class I MHC molecule with its bound peptide, or a class II MHC molecule with its bound peptide, is referred to as an MHC-peptide complex.
- The process by which intact proteins are degraded into peptides is referred to as antigen processing. Two major pathways of antigen processing occur within cells (Rock, K. L. and Golde, U., Ann. Rev. Immunol., 17:739-779, (1999); Watts, C., Ann. Rev. Immunol., 15:821-850, (1997)). One pathway, which is largely restricted to cells that are antigen presenting cells such as dendritic cells, macrophages, and B cells, degrades proteins that are typically phagocytosed or endocytosed into the cell. Peptides derived in this pathway typically bind to class II MHC molecules. A second pathway of antigen processing is present in essentially all cells of the body. This second pathway primarily degrades proteins that are made within the cells, and the peptides derived from this pathway primarily bind to class I MHC molecules. It is the peptides from this second pathway of antigen processing that are referred to herein. Antigen processing by this latter pathway involves polypeptide synthesis and proteolysis in the cytoplasm. The peptides produced are then transported into the endoplasmic reticulum of the cell, associate with newly synthesized class I MHC molecules, and the resulting MHC-peptide complexes are then transported to the cell surface. Peptides derived from membrane and secreted proteins have also been identified. In some cases these peptides correspond to the signal sequence of the proteins that are cleaved from the protein by the signal peptidase. In other cases, it is thought that some fraction of the membrane and secreted proteins are transported from the endoplasmic reticulum into the cytoplasm where processing subsequently occurs.
- Once bound to the class I MHC molecule and displayed on the surface of a cell, the peptides are recognized by antigen-specific receptors on CTLs. Mere expression of the class I MHC molecule itself is insufficient to trigger the CTL to kill the target cell if the antigenic peptide is not bound to the class I MHC molecule. Several methods have been developed to identify the peptides recognized by CTL, each method relying on the ability of a CTL to recognize and kill only those cells expressing the appropriate class I MHC molecule with the peptide bound to it (Rosenberg, S. A., Immunity, 10:281-287, (1999)). Such peptides can be derived from a non-self source, such as a pathogen (for example, following the infection of a cell by a bacterium or a virus) or from a self-derived protein within a cell, such as a cancerous cell. Examples of sources of self-derived proteins in cancerous cells have been reviewed (Gilboa, E., Immunity, 11:263-270, (1999); Rosenberg, S. A., Immunity, 10:281-287, (1999)) and include: (i) mutated genes; (ii) aberrantly expressed genes such as an alternative open reading frame or through an intron-exon boundary; (iii) normal genes that are selectively expressed in only the tumor and the testis; and (iv) normal differentiation genes that are expressed in the tumor and the normal cellular counterpart.
- Four different methodologies have typically been used for identifying the peptides that are recognized by CTLs. These are: (i) the genetic method; (2) motif analysis; (3) SErological analysis of REcombinant cDNA expression libraries (SEREX™); and (iv) the analytical chemistry approach or the Direct Identification of Relevant Epitopes for Clinical Therapeutics (DIREC™).
- The genetic method is an approach in which progressively smaller subsets of cDNA libraries from tumor cells are transfected into cells that express the appropriate MHC molecule but not the tumor-specific epitope. The molecular clones encoding T cell epitopes are identified by their ability to reconstitute tumor specific T cell recognition of transfected cells. The exact T cell epitope is then identified by a combination of molecular subcloning and the use of synthetic peptides based on the predicted amino acid sequence. Such methods, however, are susceptible to inadvertent identification of cross-reacting peptides, and are not capable of identifying important post-translational modifications.
- Motif analysis involves scanning a protein for peptides containing known class I MHC binding motifs, followed by synthesis and assay of the predicted peptides for their ability to be recognized by tumor-specific CTL. This approach requires prior knowledge of the protein from which the peptides are derived. This approach is also greatly hampered by the fact that not all of the predicted peptide epitopes are presented on the surface of a cell (Yewdell, J. W. and Bennink, J. R., Ann. Rev. Immunol., 17:51-88, (1999)), thus additional experimentation is required to determine which of the predicted epitopes is useful.
- The SEREX™ approach relies on using antibodies in the serum of cancer patients to screen cDNA expression libraries for a clone that expresses a protein recognized by the antibody. This methodology presumes that an antibody response will necessarily have developed in the presence of a T cell response, and thus, the identified clone is good candidate to encode a protein that can be recognized by T cells.
- DIREC™ involves a combination of cellular immunology and mass spectrometry. This approach involves the actual identification of CTL epitopes by sequencing the naturally occurring peptides associated with class I MHC molecules. In this approach, cells are first lysed in a detergent solution, the peptides associated with the class I MHC molecules are purified, and the peptides fractionated by high performance liquid chromatography (HPLC). The peptides are then used to reconstitute recognition by tumor-specific CTLs on a non-tumor cell expressing the appropriate MHC molecules. Sequencing is readily performed by tandem mass spectrometry (Henderson, R. A. et al., Proc. Natl. Acad. Sci.U.S.A, 90:10275-10279, (1993); Hogan, K. T. et al., Cancer Res., 58:5144-5150, (1998); Hunt, D. F. et al., Science, 255:1261-1263, (1992); Slingluff, C. L. Jr et al., J. Immunol., 150:2955-2963, (1993)).
- Immunization with cancer-derived, class I MHC-encoded molecule-associated peptides, or with a precursor polypeptide or protein that contains the peptide, or with a gene that encodes a polypeptide or protein containing the peptide, are forms of immunotherapy that can be employed in the treatment of cancer. These forms of immunotherapy require that immunogens be identified so that they can be formulated into an appropriate vaccine. Although a variety of cancer-derived antigens have been identified (Rosenberg, S. A., Immunity, 10:281-287, (1999)), not all of these are appropriate for broad-based immunotherapy as the expression of some peptides is limited to the tumor derived from a specific patient. Furthermore, the number of class I MHC molecules from which tumor-derived peptides have been discovered is largely restricted to HLA-A2. Thus, it would be useful to identify additional peptides that complex with class I MHC molecules other than HLA-A2. Such peptides would be particularly useful in the treatment of cancer patients who do not express the HLA-A2 molecule, HLA-A1 or HLA-A11 antigens, HLA-A1 supertypes, HLA-A2 supertypes and HLA-A11 supertypes, for example. It is also particularly useful to identify antigenic peptides that are derived from different original proteins, even if the derived peptides associate with the same class I MHC molecule. Because an active immune response can result in the outgrowth of tumor cells that have lost the expression of a particular precursor protein for a given antigenic peptide, it is advantageous to stimulate an immune response against peptides derived from more than one protein, as the chances of the tumor cell losing the expression of both proteins is the multiple of the chances of losing each of the individual proteins.
- The present invention relates to Immunogens comprising polypeptides with amino acid sequences comprising epitopic sequences selected from the sequences of SEQ ID NO: 1-791 and 1514-1533 and which immunogens facilitate a cytotoxic T lymphocyte (CTL)-mediated immune response against cancers. The present invention also relates to nucleic acid molecules that encode for the polypeptides and/or the full length proteins from which the polypeptides are derived, of such immunogens, and which can also be used to facilitate an immune response against cancer.
- The present invention provides compositions comprising the immunogen described herein, and polynucleotides that direct the synthesis of such polypeptides, whereby the oligopeptides and polypeptides of such immunogens are capable of inducing a CTL response against cells expressing a protein comprising an epitopic sequence of at least one of SEQ ID NO: 1-791 and 1514-1533. The cells are usually cancer cells, preferably carcinoma cells, most preferably ovarian carcinomas expressing such proteins.
- The present invention further relates to polynucleotides comprising the gene coding for a polypeptide of the immunogens disclosed herein.
- The present invention also provides methods that comprise contacting a lymphocyte, especially a CTL, with an immunogen of the invention under conditions that induce a CTL response against a tumor cell, and more specifically against a cancer cell. The methods may involve contacting the CTL with the immunogenic peptide in vivo, in which case the peptides, polypeptides, and polynucleotides of the invention are used as vaccines, and will be delivered as a pharmaceutical composition comprising a pharmaceutically acceptable carrier and the immunogen, typically along with an adjuvant or one or more cytokines.
- Alternatively, the immunogens of the present invention can be used to induce a CTL response in vitro. The generated CTL can then be introduced into a patient with cancer, more specifically cancer, colorectal carcinoma, ovarian carcinoma, breast carcinoma, lung carcinoma, or prostate carcinoma. Alternatively, the ability to generate CTL in vitro could serve as a diagnostic for cancer generally, including colorectal carcinoma, ovarian carcinoma, breast carcinoma, lung carcinoma, or prostate carcinoma.
- As used herein and except as noted otherwise, all terms are defined as given below.
- The term “peptide” is used herein to designate a series of amino acid residues, connected one to the other typically by peptide bonds between the alpha-amino and carbonyl groups of the adjacent amino acids. The peptides are typically 9 amino acids in length, but can be as short as 8 amino acids in length, and as long as 14 amino acids in length.
- The term “oligopeptide” is used herein to designate a series of amino acid residues, connected one to the other typically by peptide bonds between the alpha-amino and carbonyl groups of the adjacent amino acids. The length of the oligopeptide is not critical to the invention as long as the correct epitope or epitopes are maintained therein. The oligopeptides are typically less than about 30 amino acid residues in length, and greater than about 14 amino acids in length.
- The term “polypeptide” designates a series of amino acid residues, connected one to the other typically by peptide bonds between the alpha-amino and carbonyl groups of the adjacent amino acids. The length of the polypeptide is not critical to the invention as long as the correct epitopes are maintained. In contrast to the terms peptide or oligopeptide, the term polypeptide is meant to refer to protein molecules of longer than about 30 residues in length.
- A peptide, oligopeptide, protein, or polynucleotide coding for such a molecule is “immunogenic” (and thus an “immunogen” within the present invention) if it is capable of inducing an immune response. In the case of the present invention, immunogenicity is more specifically defined as the ability to induce a CTL-mediated response. Thus, an “immunogen” would be a molecule that is capable of inducing an immune response, and in the case of the present invention, a molecule capable of inducing a CTL response.
- A T cell “epitope” is a short peptide molecule that binds to a class I or II MHC molecule and that is subsequently recognized by a T cell. T cell epitopes that bind to class I MHC molecules are typically 8-14 amino acids in length, and most typically 9 amino acids in length. T cell epitopes that bind to class II MHC molecules are typically 12-20 amino acids in length. In the case of epitopes that bind to class II MHC molecules, the same T cell epitope may share a common core segment, but differ in the length of the carboxy- and amino-terminal flanking sequences due to the fact that ends of the peptide molecule are not buried in the structure of the class II MHC molecule peptide-binding cleft as they are in the class I MHC molecule peptide-binding cleft.
- There are three different genetic loci that encode for class I MHC molecules: HLA-A, HLA-B, and HLA-C. HLA-A1, HLA-A2, and HLA-A11 are examples of different class I MHC molecules that can be expressed from these loci. The present invention also involves peptides that are associated with HLA-A1 supertypes, HLA-A2 supertypes, and HLA-A11 supertypes. A supertype is a group of HLA molecules that present at least one shared epitope. MHC molecule peptides that have been found to bind to one member of the MHC allele supertype family (A1 for example) are thought to be likely to bind to other members of the same supertype family (A32 for example; see Table 1, below.
-
TABLE 1 Supertype Motif Genotypes A1 x[TI(SVLM)] A*0101, A*0102, A*2501, A*2601, A*2604, xxxxxx[WFY] A*3201, A*3601, A*4301, A*8001 A2 x[LIVMATQ] A*0201, A*0202, A*0203, A*0204, A*0205, xxxxxx[LIVMAT] A*0206, A*0207, A*6802, A*6901 A3 x[AILMVST] A*0301, A*1101, A*3101, A*3301, A*6801 xxxxxx[RK] A24 x[YF(WIVLMT)] A*2301, A*2402, A*2403, A*2404, A*3001, xxxxxx[FI(YWLM)] A*3002, A*3003 B7 x[P]xxxxxx B*0702, B*0703, B*0704, B*0705, B*1508, B*3501, [ALIMVFWY] B*3502, B*3503, B*51, B*5301, B*5401, B*5501, B*5502, B*5601, B*5602, B*6701, B*7801 B27 x[RKH]xxxxxx B*1401, B*1402, B*1503, B*1509, B*1510, B*1518, [FLY(WMI)] B*2701, B*2702, B*2703, B*2704, B*2705, B*2706, B*2707, B*2708, B*3801, B*3802, B*3901, B*3902, B*3903, B*3904, B*4801, B*4802, B*7301 B44 x[E(D)]xxxxxx B*18, B*3701, B*4001, B*4006, B*4101, B*4402, [FWYLIMVA] B*4403, B*4501, B*4901, B*5001 B58 x[AST]xxxxxx B*1516, B*1517, B*5701, B*5702, B*58 [FWY(LIV)] B62 x[QL(IVMP)] B*1301, B*1302, B*1501, B*1502, B*1506, B*1512, xxxxxx[FWY(MIV)] B*1513, B*1514, B*1519, B*1521, B*4601, B*52 - As used herein, reference to a DNA sequence includes both single stranded and double stranded DNA. Thus, the specific sequence, unless the context indicates otherwise, refers to the single strand DNA of such sequence, the duplex of such sequence with its complement (double stranded DNA) and the complement of such sequence.
- The term “coding region” refers to that portion of a gene which either naturally or normally codes for the expression product of that gene in its natural genomic environment, i.e., the region coding in vivo for the native expression product of the gene. The coding region can be from a normal, mutated or altered gene, or can even be from a DNA sequence, or gene, wholly synthesized in the laboratory using methods well known to those of skill in the art of DNA synthesis.
- The term “nucleotide sequence” refers to a heteropolymer of deoxyribonucleotides. The nucleotide sequence encoding for a particular peptide, oligopeptide, or polypeptide may be naturally occurring or they may be synthetically constructed. Generally, DNA segments encoding the peptides, polypeptides, and proteins of this invention are assembled from cDNA fragments and short oligonucleotide linkers, or from a series of oligonucleotides, to provide a synthetic gene which is capable of being expressed in a recombinant transcriptional unit comprising regulatory elements derived from a microbial or viral operon.
- The term “expression product” means that polypeptide or protein that is the natural translation product of the gene and any nucleic acid sequence coding equivalents resulting from genetic code degeneracy and thus coding for the same amino acid(s).
- The term “fragment,” when referring to a coding sequence, means a portion of DNA comprising less than the complete coding region whose expression product retains essentially the same biological function or activity as the expression product of the complete coding region.
- The term “DNA segment” refers to a DNA polymer, in the form of a separate fragment or as a component of a larger DNA construct, which has been derived from DNA isolated at least once in substantially pure form, i.e., free of contaminating endogenous materials and in a quantity or concentration enabling identification, manipulation, and recovery of the segment and its component nucleotide sequences by standard biochemical methods, for example, by using a cloning vector. Such segments are provided in the form of an open reading frame uninterrupted by internal nontranslated sequences, or introns, which are typically present in eukaryotic genes. Sequences of non-translated DNA may be present downstream from the open reading frame, where the same do not interfere with manipulation or expression of the coding regions.
- The term “primer” means a short nucleic acid sequence that is paired with one strand of DNA and provides a free 3′0H end at which a DNA polymerase starts synthesis of a deoxyribonucleotide chain.
- The term “promoter” means a region of DNA involved in binding of RNA polymerase to initiate transcription.
- The term “open reading frame (ORF)” means a series of triplets coding for amino acids without any termination codons and is a sequence (potentially) translatable into protein.
- The term “isolated” means that the material is removed from its original environment (e.g., the natural environment if it is naturally occurring). For example, a naturally-occurring polynucleotide or polypeptide present in a living animal is not isolated, but the same polynucleotide or polypeptide, separated from some or all of the coexisting materials in the natural system, is isolated. Such polynucleotides could be part of a vector and/or such polynucleotides or polypeptides could be part of a composition, and still be isolated in that such vector or composition is not part of its natural environment.
- The polynucleotides, and recombinant or immunogenic polypeptides, disclosed in accordance with the present invention may also be in “purified” form. The term “purified” does not require absolute purity; rather, it is intended as a relative definition, and can include preparations that are highly purified or preparations that are only partially purified, as those terms are understood by those of skill in the relevant art. For example, individual clones isolated from a cDNA library have been conventionally purified to electrophoretic homogeneity. Purification of starting material or natural material to at least one order of magnitude, preferably two or three orders, and more preferably four or five orders of magnitude is expressly contemplated. Furthermore, the claimed polypeptide which has a purity of preferably 0.001%, or at least 0.01% or 0.1%; and even desirably 1% by weight or greater is expressly contemplated.
- The nucleic acids and polypeptide expression products disclosed according to the present invention, as well as expression vectors containing such nucleic acids and/or such polypeptides, may be in “enriched form.” As used herein, the term “enriched” means that the concentration of the material is at least about 2, 5, 10, 100, or 1000 times its natural concentration (for example), advantageously 0.01%, by weight, preferably at least about 0.1% by weight. Enriched preparations of about 0.5%, 1%, 5%, 10%, and 20% by weight are also contemplated. The sequences, constructs, vectors, clones, and other materials comprising the present invention can advantageously be in enriched or isolated form.
- The term “active fragment” means a fragment that generates an immune response (i.e., has immunogenic activity) when administered, alone or optionally with a suitable adjuvant, to an animal, such as a mammal, for example, a rabbit or a mouse, and also including a human, such immune response taking the form of stimulating a CTL response within the recipient animal, such as a human. Alternatively, the “active fragment” may also be used to induce a CTL response in vitro.
- As used herein, the terms “portion,” “segment,” and “fragment,” when used in relation to polypeptides, refer to a continuous sequence of residues, such as amino acid residues, which sequence forms a subset of a larger sequence. For example, if a polypeptide were subjected to treatment with any of the common endopeptidases, such as trypsin or chymotrypsin, the oligopeptides resulting from such treatment would represent portions, segments or fragments of the starting polypeptide. This means that any such fragment will necessarily contain as part of its amino acid sequence a segment, fragment or portion, that is substantially identical, if not exactly identical, to a sequence of SEQ ID NO: 792-1513, which correspond to the naturally occurring, or “parent” proteins of the SEQ ID NO: 1-791 and 1514-1533. When used in relation to polynucleotides, such terms refer to the products produced by treatment of said polynucleotides with any of the common endonucleases.
- In accordance with the present invention, the term “percent identity” or “percent identical,” when referring to a sequence, means that a sequence is compared to a claimed or described sequence after alignment of the sequence to be compared (the “Compared Sequence”) with the described or claimed sequence (the “Reference Sequence”). The Percent Identity is then determined according to the following formula:
-
Percent Identity=100[1−(C/R)] - wherein C is the number of differences between the Reference Sequence and the Compared Sequence over the length of alignment between the Reference Sequence and the Compared Sequence wherein (i) each base or amino acid in the Reference Sequence that does not have a corresponding aligned base or amino acid in the Compared Sequence and (ii) each gap in the Reference Sequence and (iii) each aligned base or amino acid in the Reference Sequence that is different from an aligned base or amino acid in the Compared Sequence, constitutes a difference; and R is the number of bases or amino acids in the Reference Sequence over the length of the alignment with the Compared Sequence with any gap created in the Reference Sequence also being counted as a base or amino acid.
- If an alignment exists between the Compared Sequence and the Reference Sequence for which the percent identity as calculated above is about equal to or greater than a specified minimum Percent Identity then the Compared Sequence has the specified minimum percent identity to the Reference Sequence even though alignments may exist in which the herein above calculated Percent Identity is less than the specified Percent Identity.
- The present invention relates generally to immunogens and immunogenic compositions, and methods of use therefore, for the prevention, treatment, and diagnosis of cancer, especially carcinomas, including ovarian carcinomas. Disclosed according to the invention are immunogens comprising proteins or polypeptides whose amino acid sequences comprises one or more epitopic oligopeptides with sequences selected from the group SEQ ID NO: 1-791 and 1514-1533. In addition, the invention further relates to polynucleotides that can be used to stimulate a CTL response against cancer, and more specifically carcinoma, especially ovarian carcinomas.
- In accordance with the present invention there are disclosed specific oligopeptide sequences with amino acid sequences shown in SEQ ID NO: 1-791 and 1514-1533, which represent epitopic peptides (i.e. immunogenic oligopeptide sequences) of at least about 8 amino acids in length, preferably about 9 amino acids in length (i.e., nonapeptides), and no longer than about 10 amino acids in length and present as part of a larger structure, such as a polypeptide or full length protein.
- The polypeptides forming the immunogens of the present invention have amino acid sequences that comprise at least one stretch, possibly two, three, four, or more stretches of about 8 to 10 residues in length and which stretches differ in amino acid sequence from the sequences of SEQ ID NO: 1-791 and 1514-1533 by no more than about 1 amino acid residue, preferably a conservative amino acid residue, especially amino acids of the same general chemical character, such as where they are hydrophobic amino acids.
- Said polypeptides can be of any desired length so long as they have immunogenic activity in that they are able, under a given set of desirable conditions, to elicit in vitro or in vivo the activation of cytotoxic T lymphocytes (CTLs) (i.e., a CTL response) against a presentation of a cancer specific protein, especially a carcinoma or sarcoma specific protein, most especially MAGE D, MAGE 4, MFG-E8 or human retinoblastoma-like protein, especially when such proteins are presented along with MHC-1 proteins, such as where said proteins are presented in vitro or in vivo by an antigen presenting cell (APC). The proteins and polypeptides forming the immunogens of the present invention can be naturally occurring or may be synthesized chemically. According to the present invention the polypeptides may comprise at least one of SEQ ID NO: 792-1513.
- The present invention is also directed to an isolated polypeptide, especially one having immunogenic activity, the sequence of which comprises within it one or more stretches comprising any 2 or more of the sequences of SEQ ID NO: 1-791 and 1514-1533 and in any relative quantities and wherein said sequences may differ by one amino acid residues from the sequences of SEQ ID NO: 1-791 and 1514-1533 in any given stretch of 8 to 10 amino acid residues. Thus, within the present invention, by way of a non-limiting example only, such polypeptide may contain as part of its amino acid sequence, nonapeptide fragments having up to 8 amino acids identical to a sequence of SEQ ID NO: 1-4 such that the polypeptide comprises, in a specific embodiment, 2 segments with at least 8 residues identical to SEQ ID NO: 1 and one segment with at least 8 residues identical to SEQ ID NO: 3. In other embodiments, other combinations and permutations of the epitopic sequences disclosed herein may be part of an immunogen of the present invention or of such a polypeptide so long as any such polypeptide comprises at least 2 such epitopes, whether such epitopes are different or the same. Thus, in a specific embodiment, a polypeptide of the present invention may comprise 2 copies of the sequence of SEQ ID NO: 2 at some point or points within its length. Of course, any combinations and permutations of the epitopes disclosed herein, as long as they are present at least two in number in such polypeptides, are expressly contemplated.
- All of the epitopic peptides of SEQ ID NO: 1-791 and 1514-1533 are derived from proteins expressed by cancer cells and sequences and were identified through the method of Automated High Through-put Sequencing (HTPS). Accordingly, SEQ ID NO: 792-1513 are polypeptides that comprise at least one of SEQ ID NO: 1-791 and 1514-1533.
- Oligopeptides as disclosed herein may themselves be prepared by methods well known to those skilled in the art. (Grant, G. A., Synthetic Peptides: A User's Guide, 1992, W. H. Freeman and Company, New York; Coligan, J. E. et al, Current Protocols in Protein Science, 1999, John Wiley & Sons, Inc., New York).
- Besides the sequences of SEQ ID NO:1-791 and 1514-1533, the proteins and polypeptides forming the immunogens of the present invention may also comprise one or more other immunogenic amino acid stretches known to be associated with cancer, and more specifically with carcinomas and melanomas, including colorectal carcinoma, ovarian carcinoma, breast carcinoma, lung carcinoma, or prostate carcinoma, and which may stimulate a CTL response whereby the immunogenic peptides associate with HLA-A1 or HLA-A11, or HLA-A2, or another class I MHC (i.e., MHC-1) molecule.
- The immunogens of the present invention can be in the form of a composition of one or more of the different immunogens and wherein each immunogen is present in any desired relative abundance. Such compositions can be homogeneous or heterogeneous with respect to the individual immunogenic peptide components present therein, having only one or more than one of such peptides.
- The oligopeptides and polypeptides useful in practicing the present invention may be derived by fractionation of naturally occurring proteins by methods such as protease treatment, or they may be produced by recombinant or synthetic methodologies that are well known and clear to the skilled artisan (Ausubel, F. M. et al, Current Protocols in Molecular Biology, 1999, John Wiley & Sons, Inc., New York; Coligan, J. E. et al, Current Protocols in Protein Science, 1999, John Wiley & Sons, Inc., New York; Molecular Cloning: A Laboratory Manual, 1989, Cold Spring Harbor Laboratory Press, Cold Spring Harbor). The polypeptide may comprise a recombinant or synthetic polypeptide that comprises at least one of SEQ ID NO:1-791 and 1514-1533 which sequences may also be present in multiple copies. Thus, oligopeptides and polypeptides of the present invention may have one, two, three, or more such immunogenic peptides within the amino acid sequence of said oligopeptides and polypeptides, and said immunogenic peptides, or epitopes, may be the same or may be different, or may have any number of such sequences wherein some of them are identical to each other in amino acid sequence while others within the same polypeptide sequence are different from each other and said epitopic sequences may occur in any order within said immunogenic polypeptide sequence. The location of such sequences within the sequence of a polypeptide forming an immunogen of the invention may affect relative immunogenic activity. In addition, immunogens of the present invention may comprise more than one protein comprising the amino acid sequences disclosed herein. Such polypeptides may be part of a single composition or may themselves be covalently or non-covalently linked to each other.
- The immunogenic peptides disclosed herein may also be linked directly to, or through a spacer or linker to: an immunogenic carrier such as serum albumin, tetanus toxoid, keyhole limpet hemocyanin, dextran, or a recombinant virus particle; an immunogenic peptide known to stimulate a T helper cell type immune response; a cytokine such as interferon gamma or GMCSF; a targeting agent such as an antibody or receptor ligand; a stabilizing agent such as a lipid; or a conjugate of a plurality of epitopes to a branched lysine core structure, such as the so-called “multiple antigenic peptide” described in (Posneft, D. N. et al., J. Biol. Chem., 263:1719-1725, (1988)); a compound such as polyethylene glycol to increase the half life of the peptide; or additional amino acids such as a leader or secretory sequence, or a sequence employed for the purification of the mature sequence. Spacers and linkers are typically comprised of relatively small, neutral molecules, such as amino acids and which are substantially uncharged under physiological conditions. Such spacers are typically selected from the group of nonpolar or neutral polar amino acids, such as glycine, alanine, serine and other similar amino acids. Such optional spacers or linkers need not be comprised of the same residues and thus may be either homo- or hetero-oligomers. When present, such linkers will commonly be of length at least one or two, commonly 3, 4, 5, 6, and possibly as much as 10 or even up to 20 residues (in the case of amino acids). In addition, such linkers need not be composed of amino acids but any oligomeric structures will do as well so long as they provide the correct spacing so as to optimize the desired level of immunogenic activity of the immunogens of the present invention. The immunogen may therefore take any form that is capable of eliciting a CTL response.
- In addition, the immunogenic peptides of the present invention may be part of an immunogenic structure via attachments other than conventional peptide bonds. Thus, any manner of attaching the peptides of the invention to an immunogen of the invention, such as an immunogenic polypeptide as disclosed herein, could provide an immunogenic structure as claimed herein. Thus, immunogens, such as proteins of the invention, are structures that contain the peptides disclosed according to the present invention but such immunogenic peptides may not necessarily be attached thereto by the conventional means of using ordinary peptide bounds. The immunogens of the present invention simply contain such peptides as part of their makeup, but how such peptides are to be combined to form the final immunogen is left to the talent and imagination of the user and is in no way restricted or limited by the disclosure contained herein.
- The peptides that are naturally processed and bound to a class I MHC molecule, and which are recognized by a tumor-specific CTL, need not be the optimal peptides for stimulating a CTL response. See, for example, (Parkhurst, M. R. et al., J. Immunol., 157:2539-2548, (1996); Rosenberg, S. A. et al., Nat. Med., 4:321-327, (1998)). Thus, there can be utility in modifying a peptide, such that it more readily induces a CTL response. Generally, peptides may be modified at two types of positions. The peptides may be modified at amino acid residues that are predicted to interact with the class I MHC molecule, in which case the goal is to create a peptide that has a higher affinity for the class I MHC molecule than does the original peptide. The peptides can also be modified at amino acid residues that are predicted to interact with the T cell receptor on the CTL, in which case the goal is to create a peptide that has a higher affinity for the T cell receptor than does the original peptide. Both of these types of modifications can result in a variant peptide that is related to an original peptide, but which is better able to induce a CTL response than is the original peptide. As used herein, the term “original peptide” means an oligopeptide with the amino acid sequence selected from SEQ ID NO: 1-791 and 1514-1533.
- The original peptides disclosed herein can be modified by the substitution of one or more residues at different, possibly selective, sites within the peptide chain. Such substitutions may be of a conservative nature, for example, where one amino acid is replaced by an amino acid of similar structure and characteristics, such as where a hydrophobic amino acid is replaced by another hydrophobic amino acid. Even more conservative would be replacement of amino acids of the same or similar size and chemical nature, such as where leucine is replaced by isoleucine. In studies of sequence variations in families of naturally occurring homologous proteins, certain amino acid substitutions are more often tolerated than others, and these are often show correlation with similarities in size, charge, polarity, and hydrophobicity between the original amino acid and its replacement, and such is the basis for defining “conservative substitutions.”
- Conservative substitutions are herein defined as exchanges within one of the following five groups: Group 1—small aliphatic, nonpolar or slightly polar residues (Ala, Ser, Thr, Pro, Gly); Group 2—polar, negatively charged residues and their amides (Asp, Asn, Glu, Gln); Group 3—polar, positively charged residues (His, Arg, Lys); Group 4—large, aliphatic, nonpolar residues (Met, Leu, lie, Val, Cys); and Group 4—large, aromatic residues (Phe, Tyr, Trp).
- Less conservative substitutions might involve the replacement of one amino acid by another that has similar characteristics but is somewhat different in size, such as replacement of an alanine by an isoleucine residue. Highly nonconservative replacements might involve substituting an acidic amino acid for one that is polar, or even for one that is basic in character. Such radical substitutions cannot, however, be dismissed as potentially ineffective since chemical effects are not totally predictable and radical substitutions might well give rise to serendipitous effects not otherwise predictable from simple chemical principles.
- Of course, such substitutions may involve structures other than the common L-amino acids. Thus, D-amino acids might be substituted for the L-amino acids commonly found in the antigenic peptides of the invention and yet still be encompassed by the disclosure herein. In addition, amino acids possessing non-standard R groups (i.e., R groups other than those found in the common 20 amino acids of natural proteins) may also be used for substitution purposes to produce immunogens and immunogenic polypeptides according to the present invention.
- If substitutions at more than one position are found to result in a peptide with substantially equivalent or greater antigenic activity as defined below, then combinations of those substitutions will be tested to determine if the combined substitutions result in additive or syngeneic effects on the antigenicity of the peptide. At most, no more than 4 positions within the peptide would simultaneously be substituted.
- Based on cytotoxicity assays, an epitope is considered substantially identical to the reference peptide if it has at least 10% of the antigenic activity of the reference peptide as defined by the ability of the substituted peptide to reconstitute the epitope recognized by a CTL in comparison to the reference peptide. Thus, when comparing the lytic activity in the linear portion of the effector:target curves with equimolar concentrations of the reference and substituted peptides, the observed percent specific killing of the target cells incubated with the substituted peptide should be equal to that of the reference peptide at an effector:target ratio that is no greater than 10-fold above the reference peptide effector:target ratio at which the comparison is being made.
- Preferably, when the CTLs specific for a peptide of SEQ ID NO:1-791 and 1514-1533 are tested against the substituted peptides, the peptide concentration at which the substituted peptides achieve half the maximal increase in lysis relative to background is no more than about 1 mM, preferably no more than about 1 μM, more preferably no more than about 1 nM, and still more preferably no more than about 100 μM, and most preferably no more than about 10 μM. It is also preferred that the substituted peptide be recognized by CTLs from more than one individual, at least two, and more preferably three individuals.
- Thus, the epitopes of the present invention may be identical to naturally occurring tumor-associated or tumor-specific epitopes or may include epitopes that differ by no more than 4 residues from the reference peptide, as long as they have substantially identical antigenic activity.
- It should be appreciated that an immunogen may consist only of a peptide of SEQ ID NO:1-791 or 1514-1533, or comprise a peptide of SEQ ID NO:1-791 or 1514-1533, or comprise a plurality of peptides selected from SEQ ID NO:1-791 and 1514-1533, or comprise a polypeptide that itself comprises one or more of the epitopic peptides of SEQ ID NO: 1-791 and 1514-1533.
- The immunogenic peptides and polypeptides of the invention can be prepared synthetically, by recombinant DNA technology, or they can be isolated from natural sources such as tumor cells expressing the original protein product.
- The polypeptides and oligopeptides disclosed herein can be synthesized in solution or on a solid support in accordance with conventional techniques. Various automated peptide synthesizers are commercially available and can be used in accordance with known protocols. See, for example, (Grant, G. A., Synthetic Peptides: A User's Guide, 1992, W. H. Freeman and Company, New York; Coligan, J. E. et al, Current Protocols in Protein Science, 1999, John Wiley & Sons, Inc., New York). Fragments of polypeptides of the invention can also be synthesized as intermediates in the synthesis of a larger polypeptide.
- Recombinant DNA technology may be employed wherein a nucleotide sequence which encodes an immunogenic peptide or polypeptide of interest is inserted into an expression vector, transformed or transfected into an appropriate host cell, and cultivated under conditions suitable for expression. These procedures are well known in the art to the skilled artisan, as described in (Coligan, J. E. et al, Current Protocols in Immunology, 1999, John Wiley & Sons, Inc., New York; Ausubel, F. M. et al, Current Protocols in Molecular Biology, 1999, John Wiley & Sons, Inc., New York; Molecular Cloning: A Laboratory Manual, 1989, Cold Spring Harbor Laboratory Press, Cold Spring Harbor). Thus, recombinantly produced peptides or polypeptides can be used as the immunogens of the invention.
- The coding sequences for peptides of the length contemplated herein can be synthesized on commercially available automated DNA synthesizers using protocols that are well know in the art. See for example, (Grant, G. A., Synthetic Peptides: A User's Guide, 1992, W. H. Freeman and Company, New York; Coligan, J. E. et al, Current Protocols in Protein Science, 1999, John Wiley & Sons, Inc., New York). The coding sequences can also be modified such that a peptide or polypeptide will be produced that incorporates a desired amino acid substitution. The coding sequence can be provided with appropriate linkers, be ligated into suitable expression vectors that are commonly available in the art, and the resulting DNA or RNA molecule can be transformed or transfected into suitable hosts to produce the desired fusion protein. A number of such vectors and suitable host systems are available, and their selection is left to the skilled artisan. For expression of the fusion proteins, the coding sequence will be provided with operably linked start and stop codons, promoter and terminator regions, and a replication system to provide an expression vector for expression in the desired host cell. For example, promoter sequences compatible with bacterial hosts are provided in plasmids containing convenient restriction sites for insertion of the desired coding sequence. The resulting expression vectors are transformed into suitable bacterial hosts. Of course, yeast, insect, and mammalian host cells may also be used, employing suitable vectors and control sequences.
- Host cells are genetically engineered (transduced or transformed or transfected) with the vectors of this invention which may be, for example, a cloning vector or an expression vector. The vector may be, for example, in the form of a plasmid, a viral particle, a phage, etc. The engineered host cells can be cultured in conventional nutrient media modified as appropriate for activating promoters, selecting transformants or amplifying the genes of the present invention. The culture conditions, such as temperature, pH and the like, are those previously used with the host cell selected for expression, and will be apparent to the ordinarily skilled artisan.
- More particularly, the present invention also includes recombinant constructs comprising one or more of the sequences as broadly described above. The constructs comprise a vector, such as a plasmid or viral vector, into which a sequence of the invention has been inserted, in a forward or reverse orientation. In a preferred aspect of this embodiment, the construct further comprises regulatory sequences, including, for example, a promoter, operably linked to the sequence. Large numbers of suitable vectors and promoters are known to those of skill in the art, and are commercially available.
- In a further embodiment, the present invention relates to host cells containing the above-described constructs. The host cell can be a higher eukaryotic cell, such as a mammalian cell, or a lower eukaryotic cell, such as a yeast cell, or the host cell can be a prokaryotic cell, such as a bacterial cell. Introduction of the construct into the host cell can be effected by calcium phosphate transfection, DEAE-Dextran mediated transfection, or electroporation (Ausubel, F. M. et al, Current Protocols in Molecular Biology, 1999, John Wiley & Sons, Inc., New York; Molecular Cloning: A Laboratory Manual, 1989, Cold Spring Harbor Laboratory Press, Cold Spring Harbor). Such cells can routinely be utilized for assaying CTL activity by having said genetically engineered, or recombinant, host cells express the immunogenic peptides of the present invention.
- Various mammalian cell culture systems can also be employed to express recombinant protein. Examples of mammalian expression systems include the COS-7 lines of monkey kidney fibroblasts, described by Gluzman, Cell, 23:175 (1981), and other cell lines capable of expressing a compatible vector, for example, the C127, 3T3, CHO, HeLa and BHK cell lines. Mammalian expression vectors will comprise an origin of replication, a suitable promoter and enhancer, and also any necessary ribosome binding sites, polyadenylation site, splice donor and acceptor sites, transcriptional termination sequences, and 5′ flanking non-transcribed sequences. DNA sequences derived from the SV40 splice, and polyadenylation sites may be used to provide the required nontranscribed genetic elements.
- The polypeptide can be recovered and purified from recombinant cell cultures by methods including ammonium sulfate or ethanol precipitation, acid extraction, anion or cation exchange chromatography, phosphocellulose chromatography, hydrophobic interaction chromatography, affinity chromatography, hydroxylapatite chromatography and lectin chromatography. Protein refolding steps can be used, as necessary, in completing configuration of the mature protein. High performance liquid chromatography (HPLC) can be employed for final purification steps.
- The immunogenic peptides of the present invention may be used to elicit CTLs ex vivo from either healthy individuals or from cancer patients with cancer, such as colorectal carcinoma, lung carcinoma, ovarian carcinoma, breast carcinoma, or prostate carcinoma. Such responses are induced by incubating in tissue culture the individual's CTL precursor lymphocytes together with a source of antigen presenting cells and the appropriate immunogenic peptide. Examples of suitable antigen presenting cells include dendritic cells, macrophages, and activated B cells. Typically, the peptide at concentrations between 10 and 40 μg/ml, would be pre-incubated with the antigen presenting cells for periods ranging from 1 to 18 hrs. β2-microglobulin (4 μg/ml) can be added during this time period to enhance binding. The antigen presenting cells may also be held at room temperature during the incubation period (Ljunggren, H.-G. et al., Nature, 346:476-480, (1990)) or pretreated with acid (Zeh, H. J., III et al., Hum. Immunol., 39:79-86, (1994)) to promote the generation of denatured class I MHC molecules which can then bind the peptide. The precursor CTLs (responders) are then added to the antigen presenting cells to which the immunogenic peptide has bound (stimulators) at responder to stimulator ratios of between 5:1 and 50:1, and most typically between 10:1 and 20:1. The co-cultivation of the cells is carried out at 37° C. in RPMI 1640, 10% fetal bovine serum, 2 mM L-glutamine, and IL-2 (5-20 Units/ml). Other cytokines, such as IL-1, IL-7, and IL-12 may also be added to the culture. Fresh IL-2-containing media is added to the cultures every 2-4 days, typically by removing one-half the old media and replenishing it with an equal volume of fresh media. After 7-10 days, and every 7-10 days thereafter, the CTL are re-stimulated with antigen presenting cells to which immunogenic peptide has been bound as described above. Fresh IL-2-containing media is added to the cells throughout their culture as described above. Three to four rounds of stimulation, and sometimes as many five to eight rounds of stimulation, are required to generate a CTL response that can then be measured in vitro. The above described protocol is illustrative only and should not be considered limiting. Many in vitro CTL stimulation protocols have been described and the choice of which one to use is well within the knowledge of the skilled artisan. The peptide-specific CTL can be further expanded to large numbers by treatment with anti-CD3 antibody. For example, see (Riddell, S. R. and Greenberg, P. D., J. Immunol. Methods, 128:189-201, (1990); Walter, E. A. et al., N. Engl. J. Med., 333:1038-1044, (1995)).
- Antigen presenting cells that are to be used to stimulate a CTL response are typically incubated with peptide of an optimal length, most commonly a nonapeptide, that allows for direct binding of the peptide to the class I MHC molecule without additional processing. Larger oligopeptides and polypeptides are generally ineffective in binding to class I MHC molecules as they are not efficiently processed into an appropriately sized peptide in the extracellular milieu. There a variety of approaches that are known in the art, however, that allow oligopeptides and polypeptides to be exogenously acquired by a cell, which then allows for their subsequent processing and presentation by a class I MHC molecule. Representative, but non-limiting examples of such approaches include electroporation of the molecules into the cell (Harding, C. H. III, Eur. J. Immunol., 22:1865-1869, (1992)), encapsulation of the molecules in liposomes which are fused to the cells of interest (Reddy, R. et al., J. Immunol. Methods, 141:157-163, (1991)), or osmotic shock in which the molecules are taken up via pinocytosis (Moore, M. W. et al., Cell, 54:777-785, (1988)). Thus, oligopeptides and polypeptides that comprise one or more of the peptides of the invention can be provided to antigen presenting cells in such a fashion that they are delivered to the cytoplasm of the cell, and are subsequently processed to allow presentation of the peptides.
- Antigen presenting cells suitable for stimulating an in vitro CTL response that is specific for one or more of the peptides of the invention can also be prepared by introducing polynucleotide vectors encoding the sequences into the cells. These polynucleotides can be designed such that they express only a single peptide of the invention, multiple peptides of the invention, or even a plurality of peptides of the invention. There are a variety of approaches that are known in the art, that allow polynucleotides to be introduced and expressed in a cell, thus providing one or more peptides of the invention to the class I MHC molecule binding pathway. Representative, but non-limiting examples of such approaches include the introduction of plasmid DNA through particle-mediated gene transfer or electroporation (Tuting, T. et al., J. Immunol., 160:1139-1147, (1998)), or the transduction of cells with an adenovirus expressing the polynucleotide of interest (Perez-Diez, A. et al., Cancer Res., 58:5305-5309, (1998)). Thus, oligonucleotides that code for one or more of the peptides of the invention can be provided to antigen presenting cells in such a fashion that the peptides associate with class I MHC molecules and are presented on the surface of the antigen presenting cell, and consequently are available to stimulate a CTL response.
- By preparing the stimulator cells used to generate an in vitro CTL response in different ways, it is possible to control the peptide specificity of CTL response. For example, the CTLs generated with a particular peptide will necessarily be specific for that peptide Likewise, CTLs that are generated with a polypeptide or polynucleotide expressing or coding for particular peptides will be limited to specificities that recognize those peptides. More broadly, stimulator cells, and more specifically dendritic cells, can be incubated in the presence of the whole protein. As a further alternative, stimulator cells, and more specifically dendritic cells, can be transduced or transfected with RNA or DNA comprising the polynucleotide sequence encoding the protein. Under these alternative conditions, peptide epitopes that are naturally cleaved out of the protein, and which are generated in addition to peptide epitopes of SEQ ID NO:1-791 and 1514-1533 can associate with an appropriate class I MHC molecule, which may or may not include HLA-A1, -A2, or -A3. The selection of antigen presenting cells and the type of antigen with which to stimulate the CTL, is left to the ordinary skilled artisan.
- In certain embodiments, the methods of the present invention include a method for inducing a CTL response in vitro that is specific for a tumor cell expressing a molecule from A1, A2, or A3 supertypes (A11 is a member of the A3 supertype), whereby the method comprises contacting a CTL precursor lymphocyte with an antigen presenting cell that has bound an immunogen comprising one or more of the peptides disclosed according to the invention.
- In specific embodiments, the methods of the present invention include a method for inducing a CTL response in vitro that is specific for a tumor cell expressing a molecule from A1, A2, or A3 supertypes, whereby the method comprises contacting a CTL precursor lymphocyte with an antigen presenting cell that has exogenously acquired an immunogenic oligopeptide or polypeptide that comprises one or more of the peptides disclosed according to the invention.
- A yet additional embodiment of the present invention is directed to a process for inducing a CTL response in vitro that is specific for a tumor cell expressing a molecule from A1, A2, or A3 supertypes, comprising contacting a CTL precursor lymphocyte with an antigen presenting cell that is expressing a polynucleotide coding for a polypeptide of the invention and wherein said polynucleotide is operably linked to a promoter.
- In specific embodiments, the methods of the present invention include a method for inducing a CTL response in vitro that is specific for a tumor cell expressing HLA-A1, HLA-A2, or HLA-A11, whereby the method comprises contacting a CTL precursor lymphocyte with an antigen presenting cell that has bound an immunogen comprising one or more of the peptides disclosed according to the invention.
- In specific embodiments, the methods of the present invention include a method for inducing a CTL response in vitro that is specific for a tumor cell expressing HLA-A1, HLA-A2, or HLA-A11, whereby the method comprises contacting a CTL precursor lymphocyte with an antigen presenting cell that has exogenously acquired an immunogenic oligopeptide or polypeptide that comprises one or more of the peptides disclosed according to the invention.
- A yet additional embodiment of the present invention is directed to a process for inducing a CTL response in vitro that is specific for a tumor cell expressing HLA-A1, HLA-A2, or HLA-A11, comprising contacting a CTL precursor lymphocyte with an antigen presenting cell that is expressing a polynucleotide coding for a polypeptide of the invention and wherein said polynucleotide is operably linked to a promoter.
- A variety of techniques exist for assaying the activity of CTL. These techniques include the labeling of target cells with radionuclides such as Na2 51Cr04 or 3H-thymidine, and measuring the release or retention of the radionuclides from the target cells as an index of cell death. Such assays are well-known in the art and their selection is left to the skilled artisan. Alternatively, CTL are known to release a variety of cytokines when they are stimulated by an appropriate target cell, such as a tumor cell expressing the relevant class I MHC molecule and the corresponding peptide. Non-limiting examples of such cytokines include IFN-γ, TNFα, and GM-CSF. Assays for these cytokines are well known in the art, and their selection is left to the skilled artisan. Methodology for measuring both target cell death and cytokine release as a measure of CTL reactivity are given in (Coligan, J. E. et al, Current Protocols in Immunology, 1999, John Wiley & Sons, Inc., New York).
- After expansion of the antigen-specific CTLs, the latter are then adoptively transferred back into the patient, where they will destroy their specific target cell. The utility of such adoptive transfer is demonstrated in North, R. J. et al. (Infect. Immun., 67:2010-2012, (1999)) and Riddell, S. R. et al. (Science, 257:238-241, (1992)). In determining the amount of cells to reinfuse, the skilled physician will be guided by the total number of cells available, the activity of the CTL as measured in vitro, and the condition of the patient. Preferably, however, about 1×106 to about 1×1012, more preferably about 1×108 to about 1×1011, and even more preferably, about 1×109 to about 1×1010 peptide-specific CTL are infused. Methodology for reinfusing the T cells into a patient are well known and exemplified in U.S. Pat. No. 4,844,893 to Honski, et al., and U.S. Pat. No. 4,690,915 to Rosenberg.
- The peptide-specific CTL can be purified from the stimulator cells prior to infusion into the patient. For example, monoclonal antibodies directed towards the cell surface protein CD8, present on CTL, can be used in conjunction with a variety of isolation techniques such as antibody panning, flow cytometric sorting, and magnetic bead separation to purify the peptide-specific CTL away from any remaining non-peptide specific lymphocytes or from the stimulator cells. These methods are well known in the art, and are their selection is left to the skilled artisan. It should be appreciated that generation of peptide-specific CTL in this manner, obviates the need for stimulating the CTL in the presence of tumor. Thus, there is no chance of inadvertently reintroducing tumor cells into the patient.
- Thus, one embodiment of the present invention relates to a process for treating a subject with cancer characterized by tumor cells expressing complexes of a molecule from A1, A2, or A3 supertypes, for example, HLA-A1, HLA-A2, or HLA-A11, whereby CTLs produced in vitro according to the present invention are administered in an amount sufficient to destroy the tumor cells through direct lysis or to effect the destruction of the tumor cells indirectly through the elaboration of cytokines.
- Another embodiment of the present invention is directed to a process for treating a subject with cancer characterized by tumor cells expressing any class I MHC molecule and an epitope of SEQ ID NO: 1-791 and 1514-1533, whereby the CTLs are produced in vitro and are specific for the epitope or original protein and are administered in an amount sufficient to destroy the tumor cells through direct lysis or to effect the destruction of the tumor cells indirectly through the elaboration of cytokines.
- In the foregoing embodiments the cancer to be treated may include a colorectal carcinoma, an ovarian carcinoma, a breast carcinoma, a lung carcinoma, and prostate carcinoma, but especially ovarian carcinoma.
- The ex vivo generated CTL can be used to identify and isolate the T cell receptor molecules specific for the peptide. The genes encoding the alpha and beta chains of the T cell receptor can be cloned into an expression vector system and transferred and expressed in naive T cells from peripheral blood, T cells from lymph nodes, or T lymphocyte progenitor cells from bone marrow. These T cells, which would then be expressing a peptide-specific T cell receptor, would then have anti-tumor reactivity and could be used in adoptive therapy of cancer, and more specifically cancer, colorectal carcinoma, ovarian carcinoma, breast carcinoma, lung carcinoma, and prostate carcinoma.
- In addition to their use for therapeutic or prophylactic purposes, the immunogenic peptides of the present invention are useful as screening and diagnostic agents. Thus, the immunogenic peptides of the present invention, together with modern techniques of gene screening, make it possible to screen patients for the presence of genes encoding such peptides on cells obtained by biopsy of tumors detected in such patients. The results of such screening may help determine the efficacy of proceeding with the regimen of treatment disclosed herein using the immunogens of the present invention.
- Alternatively, the immunogenic peptides disclosed herein, as well as functionally similar homologs thereof, may be used to screen a sample for the presence of CTLs that specifically recognize the corresponding epitopes. The lymphocytes to be screened in this assay will normally be obtained from the peripheral blood, but lymphocytes can be obtained from other sources, including lymph nodes, spleen, tumors, and pleural fluid. The peptides of the present invention may then be used as a diagnostic tool to evaluate the efficacy of the immunotherapeutic treatments disclosed herein. Thus, the in vitro generation of CTL as described above would be used to determine if patients are likely to respond to the peptide in vivo. Similarly, the in vitro generation of CTL could be done with samples of lymphocytes obtained from the patient before and after treatment with the peptides. Successful generation of CTL in vivo should then be recognized by a correspondingly easier ability to generate peptide-specific CTL in vitro from lymphocytes obtained following treatment in comparison to those obtained before treatment.
- The oligopeptides of the invention, such as SEQ ID NO: 1-791 and 1514-1533, can also be used to prepare class I MHC tetramers which can be used in conjunction with flow cytometry to quantitate the frequency of peptide-specific CTL that are present in a sample of lymphocytes from an individual. Specifically, for example, class I MHC molecules comprising peptides of SEQ ID NO: 1-791 and 1514-1533, would be combined to form tetramers as exemplified in U.S. Pat. No. 5,635,363. Said tetramers would find use in monitoring the frequency of CTLs in the peripheral blood, lymph nodes, or tumor mass of an individual undergoing immunotherapy with the peptides, proteins, or polynucleotides of the invention, and it would be expected that successful immunization would lead to an increase in the frequency of the peptide-specific CTL.
- As stated above, a vaccine in accordance with the present invention may include one or more of the hereinabove described polypeptides or active fragments thereof, or a composition, or pool, of immunogenic peptides disclosed herein. When employing more than one polypeptide or active fragment, two or more polypeptides and/or active fragments may be used as a physical mixture or as a fusion of two or more polypeptides or active fragments. The fusion fragment or fusion polypeptide may be produced, for example, by recombinant techniques or by the use of appropriate linkers for fusing previously prepared polypeptides or active fragments.
- The immunogenic molecules of the invention, including vaccine compositions, may be utilized according to the present invention for purposes of preventing, suppressing or treating diseases causing the expression of the immunogenic peptides disclosed herein, such as where the antigen is being expressed by tumor cells. As used in accordance with the present invention, the term “prevention” relates to a process of prophylaxis in which an animal, especially a mammal, and most especially a human, is exposed to an immunogen of the present invention prior to the induction or onset of the disease process. This could be done where an individual has a genetic pedigree indicating a predisposition toward occurrence of the disease condition to be prevented. For example, this might be true of an individual whose ancestors show a predisposition toward certain types of cancer. Alternatively, the immunogen could be administered to the general population as is frequently done for infectious diseases. Alternatively, the term “suppression” is often used to describe a condition wherein the disease process has already begun but obvious symptoms of said condition have yet to be realized. Thus, the cells of an individual may have become cancerous but no outside signs of the disease have yet been clinically recognized. In either case, the term prophylaxis can be applied to encompass both prevention and suppression. Conversely, the term “treatment” is often utilized to mean the clinical application of agents to combat an already existing condition whose clinical presentation has already been realized in a patient. This would occur where an individual has already been diagnosed as having a tumor.
- It is understood that the suitable dosage of an immunogen of the present invention will depend upon the age, sex, health, and weight of the recipient, the kind of concurrent treatment, if any, the frequency of treatment, and the nature of the effect desired. However, the most preferred dosage can be tailored to the individual subject, as determined by the researcher or clinician. The total dose required for any given treatment will commonly be determined with respect to a standard reference dose as set by a manufacturer, such as is commonly done with vaccines, such dose being administered either in a single treatment or in a series of doses, the success of which will depend on the production of a desired immunological result (i.e., successful production of a CTL-mediated response to the antigen, which response gives rise to the prevention and/or treatment desired). Thus, the overall administration schedule must be considered in determining the success of a course of treatment and not whether a single dose, given in isolation, would or would not produce the desired immunologically therapeutic result or effect.
- The therapeutically effective amount of a composition containing one or more of the immunogens of this invention, is an amount sufficient to induce an effective CTL response to the antigen and to cure or arrest disease progression. Thus, this dose will depend, among other things, on the identity of the immunogens used, the nature of the disease condition, the severity of the disease condition, the extent of any need to prevent such a condition where it has not already been detected, the manner of administration dictated by the situation requiring such administration, the weight and state of health of the individual receiving such administration, and the sound judgment of the clinician or researcher. Thus, for purposes of prophylactic or therapeutic administration, effective amounts would generally lie within the range of from 1.0 μg to about 5,000 μg of peptide for a 70 kg patient, followed by boosting dosages of from about 1.0 μg to about 1,000 μg of peptide pursuant to a boosting regimen over days, weeks or even months, depending on the recipient's response and as necessitated by subsequent monitoring of CTL-mediated activity within the bloodstream. Of course, such dosages are to be considered only a general guide and, in a given situation, may greatly exceed such suggested dosage regimens where the clinician believes that the recipient's condition warrants more a aggressive administration schedule. Needless to say, the efficacy of administering additional doses, and of increasing or decreasing the interval, may be re-evaluated on a continuing basis, in view of the recipient's immunocompetence (for example, the level of CTL activity with respect to tumor-associated or tumor-specific antigens).
- For such purposes, the immunogenic compositions according to the present invention may be used against a disease condition such as cancer by administration to an individual by a variety of routes. The composition may be administered parenterally or orally, and, if parenterally, either systemically or topically. Parenteral routes include subcutaneous, intravenous, intradermal, intramuscular, intraperitoneal, intranasal, transdermal, or buccal routes. One or more such routes may be employed. Parenteral administration can be, for example, by bolus injection or by gradual perfusion over time.
- Generally, vaccines are prepared as injectables, in the form of aqueous solutions or suspensions. Vaccines in an oil base are also well known such as for inhaling. Solid forms which are dissolved or suspended prior to use may also be formulated. Pharmaceutical carriers, diluents and excipients are generally added that are compatible with the active ingredients and acceptable for pharmaceutical use.
- Examples of such carriers include, but are not limited to, water, saline solutions, dextrose, or glycerol. Combinations of carriers may also be used. These compositions may be sterilized by conventional, well known sterilization techniques including sterile filtration. The resulting solutions may be packaged for use as is, or the aqueous solutions may be lyophilized, the lyophilized preparation being combined with sterile water before administration. Vaccine compositions may further incorporate additional substances to stabilize pH, or to function as adjuvants, wetting agents, or emulsifying agents, which can serve to improve the effectiveness of the vaccine.
- The concentration of the CTL stimulatory peptides of the invention in pharmaceutical formulations are subject to wide variation, including anywhere from less than 0.01% by weight to as much as 50% or more. Factors such as volume and viscosity of the resulting composition must also be considered. The solvents, or diluents, used for such compositions include water, possibly PBS (phosphate buffered saline), or saline itself, or other possible carriers or excipients.
- The immunogens of the present invention may also be contained in artificially created structures such as liposomes, ISCOMS, slow-releasing particles, and other vehicles which increase the immunogenicity and/or half-life of the peptides or polypeptides in serum. Liposomes include emulsions, foams, micelies, insoluble monolayers, liquid crystals, phospholipid dispersions, lamellar layers and the like. Liposomes for use in the invention are formed from standard vesicle-forming lipids which generally include neutral and negatively charged phospholipids and a sterol, such as cholesterol. The selection of lipids is generally determined by considerations such as liposome size and stability in the blood. A variety of methods are available for preparing liposomes as reviewed, for example, by (Coligan, J. E. et al, Current Protocols in Protein Science, 1999, John Wiley & Sons, Inc., New York) and see also U.S. Pat. Nos. 4,235,871, 4,501,728, 4,837,028, and 5,019,369.
- Liposomes containing the peptides or polypeptides of the invention can be directed to the site of lymphoid cells where the liposomes then deliver the selected immunogens directly to antigen presenting cells. Targeting can be achieved by incorporating additional molecules such as proteins or polysaccharides into the outer membranes of said structures, thus resulting in the delivery of the structures to particular areas of the body, or to particular cells within a given organ or tissue. Such targeting molecules may a molecule that binds to receptor on antigen presenting cells. For example an antibody that binds to CD80 could be used to direct liposomes to dendritic cells.
- The immunogens of the present invention may also be administered as solid compositions. Conventional nontoxic solid carriers including pharmaceutical grades of mannitol, lactose, starch, magnesium, cellulose, glucose, sucrose, sodium saccharin, and the like. Such solid compositions will often be administered orally, whereby a pharmaceutically acceptable nontoxic composition is formed by incorporating the peptides and polypeptides of the invention with any of the carriers listed above. Generally, such compositions will contain 10-95% active ingredient, and more preferably 25-75% active ingredient.
- Aerosol administration is also an alternative, requiring only that the immunogens be properly dispersed within the aerosol propellant. Typical percentages of the peptides or polypeptides of the invention are 0.01%-20% by weight, preferably 1%-10%. The use of a surfactant to properly disperse the immunogen may be required. Representative surfactants include the esters or partial esters of fatty acids containing from 6 to 22 carbon atoms, such as caproic, octanoic, lauric, palmitic, stearic, linoleic, linolenic, olesteric and oleic acids with an aliphatic polyhydric alcohol or its cyclic anhydride. Mixed esters, such as mixed or natural glycerides may be employed. The surfactant may constitute 0.1-20% by weight of the composition, preferably 0.25-5%. Typical propellants for such administration may include esters and similar chemicals but are by no means limited to these. A carrier, such as lecithin for intranasal delivery, may also be included.
- The peptides and polypeptides of the invention may also be delivered with an adjuvant. Adjuvants include, but are not limited to complete or incomplete Freund's adjuvant, Montanide ISA-51, Lymphocyte Activation Gene-3 (LAG-)3, aluminum phosphate, aluminum hydroxide, alum, and saponin. Adjuvant effects can also be obtained by injecting a variety of cytokines along with the immunogens of the invention. These cytokines include, but are not limited to IL-1, IL-2, IL-7, IL-12, and GM-CSF.
- The peptides and polypeptides of the invention can also be added to professional antigen presenting cells such as dendritic cells that have been prepared ex vivo. For example, the dendritic cells could be prepared from CD34 positive stem cells from the bone marrow, or they could be prepared from CD14 positive monocytes obtained from the peripheral blood. The dendritic cells are generated ex vivo using cytokines such as GM-CSF, IL-3, IL-4, TNF, and SCF. The cultured DC are then pulsed with peptides at various concentrations using standard methods that are well known in the art. The peptide-pulsed dendritic cells can then be administered either intraveneously, subcutaneously, or intradermally, and the immunization may also include cytokines such as IL-2 or IL-12.
- The present invention is also directed to a vaccine in which an immunogen of the present invention is delivered or administered in the form of a polynucleotide encoding the a polypeptide or active fragment as disclosed herein, whereby the peptide or polypeptide or active fragment is produced in vivo. The polynucleotide may be included in a suitable expression vector and combined with a pharmaceutically acceptable carrier. For example, the peptides or polypeptides could be expressed in plasmid DNA and nonreplicative viral vectors such as vaccinia, fowlpox, Venezuelan equine encephalitis virus, adenovirus, or other RNA or DNA viruses. These examples are meant to be illustrative only and should not be viewed as self-limiting A wide variety of other vectors are available and are apparent to those skilled in the art from the description given herein. In this approach, a portion of the nucleotide sequence of the viral vector is engineered to express the peptides or polypeptides of the invention. Vaccinia vectors and methods useful in immunization protocols are described in U.S. Pat. No. 4,722,848, the disclosure of which is incorporated herein by reference in its entirety.
- Regardless of the nature of the composition given, additional therapeutic agents may also accompany the immunogens of the present invention. Thus, for purposes of treating tumors, compositions containing the immunogens disclosed herein may, in addition, contain other antitumor pharmaceuticals. The use of such compositions with multiple active ingredients is left to the discretion of the clinician.
- In addition, the immunogens of the present invention can be used to stimulate the production of antibodies for use in passive immunotherapy, for use as diagnostic reagents, and for use as reagents in other processes such as affinity chromatography.
- The present invention also relates to antibodies that react with immunogens, such as a polypeptide comprising one or more of the epitopic peptides of SEQ ID NO: 1-791 and 1514-1533 as disclosed herein. Active fragments of such antibodies are also specifically contemplated. Such antibodies, and active fragments of such antibodies, for example, and Fab structure, may react with, including where it is highly selective or specific for, an immunogenic structure comprising 2, 3, 4 or more of the epitopic peptides of the invention.
- With the advent of methods of molecular biology and recombinant technology, it is now possible to produce antibody molecules by recombinant means and thereby generate gene sequences that code for specific amino acid sequences found in the polypeptide structure of the antibodies. Such antibodies can be produced by either cloning the gene sequences encoding the polypeptide chains of said antibodies or by direct synthesis of said polypeptide chains, with in vitro assembly of the synthesized chains to form active tetrameric (H2L2) structures with affinity for specific epitopes and antigenic determinants. This has permitted the ready production of antibodies having sequences characteristic of neutralizing antibodies from different species and sources.
- Regardless of the source of the antibodies, or how they are recombinantly constructed, or how they are synthesized, in vitro or in vivo, using transgenic animals, such as cows, goats and sheep, using large cell cultures of laboratory or commercial size, in bioreactors or by direct chemical synthesis employing no living organisms at any stage of the process, all antibodies have a similar overall 3 dimensional structure.
- This structure is often given as H2L2 and refers to the fact that antibodies commonly comprise 2 light (L) amino acid chains and 2 heavy (H) amino acid chains. Both chains have regions capable of interacting with a structurally complementary antigenic target. The regions interacting with the target are referred to as “variable” or “V” regions and are characterized by differences in amino acid sequence from antibodies of different antigenic specificity.
- The variable regions of either H or L chains contains the amino acid sequences capable of specifically binding to antigenic targets. Within these sequences are smaller sequences dubbed “hypervariable” because of their extreme variability between antibodies of differing specificity. Such hypervariable regions are also referred to as “complementarity determining regions” or “CDR” regions. These CDR regions account for the basic specificity of the antibody for a particular antigenic determinant structure.
- The CDRs represent non-contiguous stretches of amino acids within the variable regions but, regardless of species, the positional locations of these critical amino acid sequences within the variable heavy and light chain regions have been found to have similar locations within the amino acid sequences of the variable chains. The variable heavy and light chains of all antibodies each have 3 CDR regions, each non-contiguous with the others (termed L1, L2, L3, H1, H2, H3) for the respective light (L) and heavy (H) chains. The accepted CDR regions have been described in the text and figures of Kabat et al. (J. Biol. Chem. 252:6609-6616 (1977)).
- In all mammalian species, antibody polypeptides contain constant (i.e., highly conserved) and variable regions, and, within the latter, there are the CDRs and the so-called “framework regions” made up of amino acid sequences within the variable region of the heavy or light chain but outside the CDRs.
- The antibodies disclosed according to the invention may also be wholly synthetic, wherein the polypeptide chains of the antibodies are synthesized and, possibly, optimized for binding to the polypeptides disclosed herein as being receptors. Such antibodies may be chimeric or humanized antibodies and may be fully tetrameric in structure, or may be dimeric and comprise only a single heavy and a single light chain. Such antibodies may also include fragments, such as Fab and F(ab2)′ fragments, capable of reacting with and binding to any of the polypeptides disclosed herein as being receptors.
- A further embodiment of the present invention relates to a method for inducing a CTL response in a subject comprising administering to subjects that express HLA-A1 antigens an effective (i.e., CTL-stimulating amount) of an immunogen of the invention that does not comprise the entire protein expressing the epitopic peptides disclosed herein (i.e., one that comprises less than the entire protein where the protein is a naturally occurring polypeptide) in an amount sufficient to induce a CTL response to tumor cells expressing at least HLA-A1 or HLA-A2, as the case may be, thereby eliciting a cellular response against said tumor cells. A still further embodiment of the present invention relates to a method for inducing a CTL response in a subject, wherein the immunogen is in the form of a polynucleotide. In one non-limiting example, the method comprises administering to subjects that express HLA-A1 at least one CTL epitope, wherein said epitope or epitopes are selected from a group comprising the peptides disclosed according to the invention, and are coded within a polynucleotide sequence that does not comprise the entire protein coding region, in an amount sufficient to induce a CTL response to tumor cells expressing HLA-A1 or HLA-A2.
- While the below examples are provided to illustrate the invention, it is to be understood that these methods and examples in no way limit the invention to the embodiments described herein and that other embodiments and uses will no doubt suggest themselves to those skilled in the art. All publications, patents, and patent applications cited herein are hereby incorporated by reference, as are the references cited therein. It is also to be understood that throughout this disclosure where the singular is used, the plural may be inferred and vice versa and use of either is not to be considered limiting.
- For HLA-A1 and HLA-A11 studies, ARGOV57, a HLA-A1/11 positive ovarian cell line, was established by culturing tumor cells from an ascitic fluid from an ovarian patient.
- For HLA-A2 studies, OVCAR3, a HLA-A2 positive ovarian carcinoma cell line, was established by culturing tumor cells from an ascitic fluid from an ovarian patient.
- SKOV3-A2, a HLA-A2 stably expressing ovarian carcinoma cell line, was established by culturing tumor cells from an ascitic fluid from an ovarian patient and transduced with HLA-A2 gene.
- ARGOV57 cells were grown in 10-chamber Nunc cell factories (Fisher, Pittsburgh, Pa.). The cells were harvested by treatment with 0.45% trypsin and 0.32 mM EDTA, washed two times in phosphate-buffered saline solution (pH 7.4), and stored as cell pellets at −80° C. Aliquots of 6-8×1010 cells were solubilized at 5-10×106 cells/ml in 20 mM Tris, pH 8.0, 150 mM NaCl, 1% CHAPS, 18.5 μg/ml iodoacetamide, 5 μg/ml aprotonin, 10 μg/ml leupeptin, 10 μg/ml pepstatin A, 5 mM EDTA, 0.2% sodium azide, and 17.4 μg/ml phenylmethylsulfonyl fluoride for 1 h. This and all subsequent steps were performed with ice-cold solutions and at 4° C. The lysates were then centrifuged at 100,000×g, the pellets discarded, and the supernatants passed through a 0.22 μm filter. The supernatants were then passed over a series of columns with the first containing Sepharose, and the second containing the HLA-A1-specific monoclonal antibody, GAP-A1, bound to a protein A-Sepharose matrix. The second column was then sequentially washed with 20 column volumes of 20 mM Tris, pH 8.0, 150 mM NaCl, 20 column volumes of 20 mM Tris, pH 8.0, 1.0 M NaCl, and 20 column volumes of 20 mM Tris, pH 8.0. The peptides were eluted from the column with 5 column volumes of 10% acetic acid. The isolated HLA-A1 molecules were then boiled for 5 min to further dissociate any bound peptide from the heavy chains. The peptides were then separated from the co-purifying class I heavy chain and β2-microglobulin by centrifugation on a Ultrafree-CL membrane with a nominal molecular weight cut-off of 5,000 Daltons (Millipore, Bedford, Mass.).
- For a separate study, OVCAR3 or SKOV3 cells were successfully prepared using the same procedure as just described except that HLA-A2 molecules were prepared using HLA-A2 specific antibodies.
- The peptide extracts were fractionated by RP-HPLC (Reversed Phase-High Performance Liquid Chromatography) using an Applied Biosystems (ABI) model 140B system. The extracts were concentrated by vacuum centrifugation from about 20 ml down to 250 μl and injected into either a Brownlee (Norwalk, Conn.) C18 Aquapore column (2.1 mm×3 cm; 300 Å; 7 μm) or a Higgins (Mountain View, Calif.) C18 Haisil column (2.1 mm×4 cm; 300 Å; 5 μm). The peptides were eluted by first using a gradient of acetonitrile/0.085% TFA (trifluoroacetic acid) in 0.1% TFA/water, with the concentration of acetonitrile increasing from 0-9% (0-5 minutes), 9-36% (5-55 minutes), and 36-60% (55-62 minutes). A second dimension fractionation of combined fractions 17 and 18 from the first dimension (TFA) fraction was accomplished using the same gradient but with the substitution of HFBA (heptafluorobutyric acid) for TFA. The flow rate was 200 μl/min, and fractions were collected at 1 min (Brownlee column) or 40 second (Higgins column) intervals. A third dimension of RP-HPLC was achieved using an Eldex (Napa, Calif.) MicroPro Pump, a homemade C18 microcapillary column, and an ABI model 785A UV absorbance detector. The column was prepared by packing a 27 cm bed of 10 μm C18 particles in a section of 285 μm o.d./75 μm i.d. fused silica (Polymicro Technologies, Phoenix, Ariz.). Peptides in combined fractions 26 and 27 of the second dimension fraction were loaded onto this column and eluted with a gradient of acetonitrile/0.67% triethylamine acetate/water in 0.1% triethylamine acetate/water, with the concentration of acetonitrile increasing from 0-60% in 40 minutes. The flow rate was about 300 nl/min, and fractions were collected into 25 μl of water every 30 s. In all RP-HPLC experiments, peptides were detected by monitoring UV absorbance at 214 nm.
- The second dimension HPLC fraction was analyzed using an affluent splitter on the microcapillary HPLC column. In this experiment, the column (360 μm o.d. X 100 μm i.d. with a 25 cm C18 bed) was butt connected with a zero dead volume tee (Valco, Houston, Tex.) to two pieces of fused silica of different lengths (25 μm and 40 μm i.d.). Peptides were eluted with a 34 min gradient of 0-60% acetonitrile. The 25 μm capillary deposited one-fifth of the HPLC effluent into the wells of a microtiter plate for use in CTL epitope reconstitution assays, whereas the remaining four-fifths of the effluent was directed into the mass spectrometer. Ions were formed by electrospray ionization, and mass spectra were recorded by scanning between mass to charge ratios (m/z) 300 and 1400 every 1.5 seconds. Peptide sequences were determined by CAD (collision-activated dissociation) tandem mass spectrometry as described in the literature (Hunt, D. F. et al., Proc. Natl. Acad. Sci. U.S.A, 83:6233-6237, (1986)).
- Proteins containing peptides corresponding to the masses identified by MS were analyzed with the search algorithm, SEQUEST. Searches were also carried out on the GenBank non-redundant sequence database (http://ncbi.nlm.nih.-gov/Entrez/) as well as on our own unique database of 2943 specific sequences compiled from GenBank and EST data-base entries. Upon experimental confirmation of the peptide sequence, a tBLASTn search of the GenBank non-redundant database was performed to identify any genes containing the DNA sequence encoding the peptide.
- Peptides were synthesized using a Gilson (Madison, Wis.) AMS 422 multiple peptide synthesizer. Quantities of 10 μMol were synthesized using conventional FMOC amino acids, resins, and chemical techniques. Peptides were purified by RP-HPLC using a 4.6 mm×100 mm POROS (Perseptive Biosystems, Cambridge, Mass.) column and a 10 min, 0-60% acetonitrile in 0.1% TFA gradient.
- PBMC were purified from HLA-A2+ normal donor blood using lymphocyte separation media (Cappel ICN Biomedical, Aurora, Ohio). PBMC (5.3×106) were added to individual wells of a 24-well cluster plate (Costar, Corning, N.Y.) in 1.0 ml of serum-free AIM-V medium (Life Technologies) and allowed to adhere for 60 min at 37° C. Non-adherent cells were removed and saved as a source of effector T cells. Adherent PBMC (−8.3×105/well) were then pulsed with 50 mg/ml synthetic peptides in serum-free AIM-V medium containing 1.5 mg/ml β2-microg lobulin (Calbiochem-Novabiochem, San Diego, Calif.) and incubated for 2 h at 37° C. Unbound peptides were aspirated and the wells washed with media.
- Monocyte-derived DC were generated as follows. PBMC (5.3×107) were allowed to adhere in T-75 flasks (Corning) in 10 ml of serum-free AIM-V medium for 60 min at 37° C. Non-adherent cells were collected as a source of effector T cells and pooled with the previous collection above. Adherent monocytes in flasks were then exposed to recombinant human granulocyte macrophage colony stimulating factor (GM-CSF, 25 ng/ml; Peprotech) and recombinant human IL-4 (100 ng/ml; Peprotech) in 10 ml of AIM-V medium containing 10% heat-inactivated FBS. DC obtained by this method [immature DC (iDC)] are characterized by expression of low levels of CD83, CD80, CD86, and HLA class I and class II molecules (data not shown).
- Mature DC (mDC) were obtained by exposing day 5 DC cultures to recombinant soluble CD40 ligand (sCD40L; Peprotech) at 1.5 mg/ml for 24 h in the presence of 25 ng/ml GM-CSF and are characterized by expression of high levels of CD80, CD86, and HLA class I and class II molecules. mDC were harvested, washed, pulsed with 5 mg/ml peptide in serum-free AIM-V medium and irradiated (5000 rad) prior to use as stimulators.
- The protocol used here is a modification of the method described by Plebanski et al. (Eur. J. Immunol. 25:1783, (1995)). CTL to peptide were generated by 3±4 cycles of stimulation with peptide-loaded APC. For the first round of stimulation (day 0), T cells or non-adherent PBMC from above (2.3×106/ml or 4.3×106 per well) were added in bulk (CD4+, CD8+, NK, etc.) to adherent PBMC-loaded peptides in serum-free medium (50 mg/ml), β2-microglobulin (1.5 mg/ml) (Calbiochem-Novabiochem), recombinant human IL-7 (5 ng/ml) (Peprotech) and keyhole limpet hemocyanin (5 mg/ml) (Sigma, St Louis, Mo.). Cultures were re-stimulated with iDC every 7 days, pulsed with varying amounts of peptide (second round 25 mg/ml, third round 10 mg/ml) and irradiated (5000 rad) on day 8. At each re-stimulation, the T cells were transferred to new plates by first aspirating 70% of spent media in wells and then transferring the pooled contents to a new plate. Fresh IL-7 was added at each re-stimulation. The responder:stimulator (T cell:DC) ratio was set at 20 for each stimulation. Recombinant human IL-2 (10 U/ml) was added on day 5 after each re-stimulation.
- Prior to 51Cr-release assay, the T cells were harvested and CD8+T cells were purified by positive selection using CD8+ microbeads immunomagnetic cell separation with MACS kit (Miltenyi Biotec, Auburn, Calif.). If a fourth round of stimulation was necessary following CTL analysis, the CTL were pulsed as before, except with 5±10 mg/ml of peptide.
- HLA-A2-allospecific CTL were obtained in a mixed lymphocyte reaction by repeated stimulation of HLA-A3+PBMC (responders) with irradiated HLA-A2+ stimulator PBMC at a ratio of 10:1 in the presence of 10 U/ml IL-2. Stimulation was repeated weekly with PBMC from different HLA-A2+ donors so as to minimize alloresponse to non-HLA-A2 antigens. T cells were assessed for lysis on several HLA-A2+ targets including tumor cells, EBV-B cells and HLA-A3+ targets every week after the third round of stimulation.
- Expansion of large numbers of peptide-specific or HLA-A2-allospecific CTL was achieved by culturing 5.3×104±1.3×105 T cells around day 6 or 7 post peptide- or allostimulation in the presence of 2.5-3.0×107 irradiated (5000 rad) allogeneic normal donor PBMC coated with anti-CD3 antibody at 10 ng/ml (BD PharMingen, San Diego, Calif.) and 25 U/ml of recombinant human IL-2 (Peprotech) in a final volume of 30 ml RPMI medium. Media changes with IL-2 addition (50 U/ml) were effected on days 5 and 8. Cells were harvested for cytotoxicity assays on days 10±12 and re-stimulated or frozen for later use.
- The standard 4-h Cr-release assay was performed in 96-well V-bottomed microplates. Target cells in suspension (T2, C1R.A2, B-LCL and K562) were labeled with 100 mCi Na2 51CrO4 (NEN Life Science, Boston, Mass.) per 1.3×106 cells either overnight (˜6±18 h) in 5 ml RPMI 1640 media containing 2±5% FBS or for 60±90 min at 37° C. directly with the cell pellet in the case of adherent cells (tumor cell lines and control lines). Labeling was terminated by washing the targets with cold media containing 5% FBS for a total of three washes. Target cells were resuspended at a concentration of 2−3×104/ml. About 2−3×103 targets in 100 ml were delivered to each well containing CTL (effectors) seeded at different E:T ratios. Spontaneous release wells contained targets in media alone, while maximal release wells contained targets in 2% NP-40 detergent (Igepal CA-630; Sigma). HLA restriction of CTL-mediated killing was achieved by preincubation of targets with HLA-specific antibodies prior to incubation with CTL.
- The plate was gently spun for 1±2 min and incubated at 37° C. for 4 h. For harvesting assay plates, 100 ml of supernatants from the wells was transferred to counting tubes (USA Scientific) and g counts were determined in a g counter (ICN Micromedic Systems, Huntsville, Ala.). Cytolytic activity of T cells was expressed in percent specific lysis as follows: specific lysis={[experimental release (c.p.m.)±spontaneous release (c.p.m.)]/[maximal release (c.p.m.)±spontaneous release (c.p.m.)]}.
- Peptide-stimulated CTL were reacted with 51Cr-labeled Ov2 tumor cells (E:T ratio of 40) in the presence of excess of cold targets in a 4-h Cr-release assay. Cold targets were either empty T2 cells, T2 cells pulsed with 1 mg/ml relevant peptide (used to stimulate CTL) or irrelevant (control) peptides (HER-2/neu 369±377 or MART 127±35), or IFN-γ pre-treated tumor cells (SKOV3.A2 and OVCAR 3) with the cold target in 5-fold excess of the hot target. Results indicate that (i) CTL show specific interaction with the peptide to which they are sensitized to, and (ii) CTL compete for similar epitopes presented on Ov2 as were found in SKOV3.A2 and OVCAR3 cell lines by MS.
-
TABLE 2 Description of Fragments, Parent Sequence Identification and Parent SwissProt Identification Number for peptides 1-791 and 1514-1533 Parent SEQ SwissProt ID Identification NO: Fragment Parent Sequence Identification No. 1 AEAEFYRQV BCL-6 corepressor long isoform— Q6W2J9 2 IYNGDMEKI E1B_19K/Bcl-2-interacting protein Q12983 Nip3 3 KEFDGKSLV Similar to Heat shock protein HSP P08238 90-beta (HSP 84)(HSP 90) 4 HIPAGTLVQV Cytochrome P450 11B2, P19099 mitochondrial precursor 5 SLAEGLRTV 2′-5′oligoadenylate synthetase 3 Q2HJ14 6 YLGDGPKLV 26S protease regulatory subunit 4 P62191 (P26s4) 7 YLASLIRSV 26S proteasome non-ATPase P51665 regulatory subunit 7 8 FVDDYTVRV 26S proteasome non-ATPase O00487 regulatory subunit 14 9 KLLEPVLLL 40S ribosomal protein S16 P62249 10 KLIEVDDERKL 40S ribosomal protein S6 P62753 (Phosphoprotein NP33) 11 RLFEGNALL 40S ribosomal protein S9 P46781 12 TLYEAVREV 60S ribosomal protein L10a (CSA- P62906 19) 13 NMVAKVDEV 60S ribosomal protein L10a (CSA- P62906 19) 14 SLIKQIPRI 60S ribosomal protein L10a (CSA P62906 19) 15 FLSEEGGHVAV 6-phosphofructo-2-kinase/fructose- Q16877 2,6-biphosphatase 4 (6PF-2-K/Fru- 2,6-P2ASE testis-type isozyme) 16 IETINFHEV Cleavage and polyadenylation Q9UKF6 specificity factor, 73 kDa subunit (CPSF 73 kDa subunit) 17 YLNDLIHSV A kinase anchor protein 10, O43572 mitochondrial precursor 18 RVAPEEHPVL Actin, cytoplasmic 1 (Beta-actin) P60709 19 DVLKIPVQLV Activated T-cell marker CD109 Q6YHK3 20 LSDFLKANV Activin receptor type 2A precursor P27037 (EC 2.7.11.30) 21 DLCFEKVNV ADAM19 protein Q8TBU7 22 KLHDINAQL AP-1 complex subunit beta-1 Q10567 (Adapter-related protein complex 1 beta-1 subunit)(Beta-adaptin 1) 23 GNGAPDVFQT Adaptor-related protein NF01019537 Q9BYI8 24 IDAIRIPVL Lung alpha/beta hydrolase protein 1 Q96SE0 25 FIASKGVKLV Alpha-actinin-3 Q08043 26 HRPDLIDY Alpha-actinin-3 Q08043 27 SPQGLELALPS Ankyrin-2 (Brain ankyrin)(Ankyrin- Q01484 B) 28 KIVKRPSLQFL Ankyrin repeat and SOCS box Q8WXJ9 protein 17 29 TLVTVSAAKT Anti-colorectal carcinoma heavy Q65ZQ1 chain 30 KVLDGSPIEV APOBEC1 complementation factor Q9NQ94 (APOBEC1-stimulating protein) 31 FLAEHPNVTL Probable DNA dC->dU-editing Q96AK3 enzyme APOBEC-3D (EC 3.5.4.-) 32 NLVQDSLDL Apolipoprotein L4 precursor Q9BPW4 (Apolipoprotein L-IV) 33 ISENEKLQK Apoptosis stimulating of p53 protein Q96KQ4 1 34 VLAARNPAKV Nucleoporin 188 kDa (arachin) Q5SRE5 35 RYFDGNLEKL Protein ariadne-1 homolog (ARI-1) Q9Y4X5 (Ubiquitin-conjugating enzyme E2- binding protein 1) 36 TLADVLYHV Set1/Ash2 histone methyltransferase Q9UBL3 complex subunit ASH2 (ASH2-like protein) 37 LPSPKPMKMKN ATP synthase F0 subunit 8 Q85KZ3 38 ISSMLVLFF Splice isoform 2 of Q9H7F0 Q9H7F0 ATPase_family_homolog_up- regulated_in_senescence_cells— 39 SPDEGALVRA Probable phospholipid-transporting Q9Y2Q0 ATPase IA (EC 3.6.3.1)(Chromaffin granule ATPase II) 40 ILLTTLIPY ATP-binding cassette A10 Q8WWZ4 41 NLEQQETEP ATP-binding cassette sub-family A Q9BZC7 member 2 (ATP-binding cassette transporter 2)(ATP-binding cassette 2) 42 RKVLYVMEL Autoantigen RCD8 Q6P2E9 43 EAIPARKLK xonemal dynein heavy chain 8 Q96JB1 44 SLRLENITV Butyrophilin-like protein 8 precursor Q6UX41 45 SYVLKKAQV Ubiquitin carboxyl-terminal Q9Y2K6 hydrolase 20 (EC 3.1.2.15) 46 KLIHPKLEY Bardet-Biedl syndrome 7 protein Q8IWZ6 (BBS2-like protein 1) 47 EFDQLDQEN Large proline-rich protein BAT2 P48634 (HLA-B-associated transcript 2) 48 TVLLRLGDEL Bcl-2 related ovarian killer 49 LFEILIEQI Lipopolysaccharide-responsive and P50851 beige-like anchor protein (CDC4-like protein) 50 KLELDETGQE Splice isoform 3 of P35612 P35612-3 51 LAIGAFTLLL UDP-GlcNAc: betaGal beta-1,3-N- Q9Y2A9 acetylglucosaminyltransferase 3 (EC 2.4.1.-) 52 QILLDETLK Cell growth inhibiting protein 39 Q2TTR2 53 DECITNLLV BH3-interacting domain death P55957 agonist (BID) 54 TVVSGSNVTLN CD48 antigen precursor (B- P09326 lymphocyte activation marker BLAST-1) 55 SLDERPVAV Bone morphogenetic protein receptor Q13873 type-2 precursor (EC 2.7.11.30) 56 MVDSQQKSP Bullous pemphigoid antigen 1, Q8WXK8 isoform 7 57 SLLLLPEKN BRCA1 associated RING domain 1 Q53F80 variant 58 VLCVSDIISL Breast cancer type 2 susceptibility P51587 protein (Fanconi anemia group D1 protein) 59 FLPDPSALQNL Protein BRE (Brain and reproductive Q9NXR7 organ-expressed protein) (BRCA1/BRCA2-containing complex subunit 45) 60 MLNEHDFEV Breast cancer 1 early onset Q3LRJ0 61 VNTDFSPYL Breast cancer 1 early onset Q3LRJ0 62 EFMLVYKFAR Breast and ovarian cancer Q7KYU6 susceptibility protein 63 TLWVDPYEV BTG2 protein (NGF-inducible anti- P78543 proliferative protein PC3) 64 FLDHIIASV Nuclear protein 5qNCA Q7LBC6 65 TLNDREYQL CAD protein [Includes: Glutamine- P27708 dependent carbamoyl-phosphate synthase (EC 6.3.5.5); Aspartate carbamoyltransferase (EC 2.1.3.2); Dihydroorotase (EC 3.5.2.3)] 66 VEVMVNDVN Cadherin EGF LAG seven-pass G- Q9NYQ7 type receptor 3 precursor (Flamingo homolog 1)(hFmi1)(Multiple epidermal growth factor-like domains 2)(Epidermal growth factor-like 1) 67 LSIYLSIYL Cadherin FIB3 Q6UW70 68 SLSMVNHRL Integrin alpha-3 precursor P26006 (Galactoprotein B3) Calcineurin B homologous protein 2 69 RVDFPGFVR (Hepatocellular carcinoma- O43745 associated antigen 520) 70 MTDKAPPGV Calcium/calmodulin-dependent Q7Z7J9 protein kinase II inhibitor alpha (CaMKIINalpha) 71 WTNPQFKI Calpain-11 (EC 3.4.22.-) Q9UMQ6 72 IMAQLPQEQKA Alpha-1 catenin (Cadherin-associated P35221 protein)(Alpha E-catenin) 73 KIDPLEVEE Neural cell adhesion molecule variant Q59FY0 74 KLPEKWESV Ribosomal L1 domain-containing O76021 protein 1 (Cellular senescence- inhibited gene protein) 75 LIEKEKVLN CENP-F kinetochore protein P49454 (Centromere protein F)(Mitosin) 76 FEVKEDQVK Centaurin-delta 1 (Cnt-d1)(Ad- Q8WZ64 GAP, Rho-GAP, ankyrin repeat and pleckstrin homology domain- containing protein 2) 77 DTEAEKSQV Centrosomal protein 2 (Centrosomal Q9BV73 Nek2-associated protein 1)(C-NAP1) 78 FLKEHMDEV Pericentriol material 1 Q15154 79 KLLGELHTL Pericentriol material 1 Q15154 80 TLVEAFPTL Cervical cancer suppressor gene 5 Q8NFX8 81 QSNKGFVVIN T-complex protein 1 subunit zeta-2 Q92526 82 LADGALIYR Chemokine-like factor (C32) Q9UBR5 83 GLGAEIEIR Vacuolar protein sorting 13A Q96RL7 84 GKLILLDKL Chromodomain-helicase-DNA- O14647 binding protein 2 (EC 3.6.1.-) 85 PQTICRKP FERM domain-containing protein 6 Q96NE9 86 RSYYLNEI Putative protein C21orf56 Q9H0A9 87 TTITVSPFY Adiponutrin (iPLA2-epsilon) Q9NST1 88 RLPDDDPTAV Coatomer subunit gamma-2 Q9UBF2 89 LVAISTVSFSI Sodium/potassium/calcium Q9UI40 exchanger 2 precursor 90 VLIDYQRNV Exportin-1 (Chromosome region 014980 maintenance 1 protein homolog) 91 SILNEGGIK CUB and sushi domain-containing Q7Z407 protein 3 precursor 92 YMADRLLGV Cullin-7 (CUL-7) Q14999 93 YLKDLIEEV Cyclic AMP-dependent transcription P18848 factor ATF-4 94 YLDIKGLLD S-phase kinase-associated protein 1A P63208 (Cyclin A/CDK2-associated protein p19) 95 PCLSELHKA Cyclin-A1 P78396 96 TVLDFGVLASI Cyclin M3, isoform 1 Q8NE01 97 MPSETPQAE Cystathionine beta-synthase human Q58H57 homolog of Cynomolgus monkey gene product 98 FLLEALRKT Cytochrome P450 2E1 (EC P05181 1.14.14.1) 99 KMLETKWSL Keratin, type II cytoskeletal 8 P05787 100 QPLLKQSPW CPEB2 protein Q3B 8N6 101 YLLPAIVHI Probable ATP-dependent RNA P17844 helicase DDX5 (EC 3.6.1.-) 102 KLLPGDIHQI Dedicator of cytokinesis protein 1 Q14185 103 SLLKGDLKGV Development and differentiation- O43150 enhancing factor 2 104 NAEVLLVSEI Probable ubiquitin carboxyl-terminal O00507 hydrolase FAF-Y (EC 3.1.2.15) 105 RLWGEPVNL Probable ubiquitin carboxyl-terminal O00507 hydrolase FAF-Y (EC 3.1.2.15) 106 QLIDLSSPLI G2 and S phase expressed protein 1 Q9NYZ3 107 YIDYTGAAYA HUMAN CDNA FLJ30829 fis, clone Q96NI3 FEBRA2001790, highly similar to Xenopus laevis RRM-containing protein SEB-4 mRNA 108 VIENKSDEKVI KIAA1799 protein Q96B95 109 PSPQLWTV Peroxisomal proliferator-activated Q9BYK8 receptor A-interacting complex 285 kDa protein (EC 3.6.1.-)(ATP- dependent helicase PRIC285) 110 EGRGGLPAGLPV HUMAN KIAA1922 Q96PW6 111 NMYGKVVTV Transcription elongation factor SPT5 O00267 (DLC-1)(deleted in liver cancer-1) 112 RLYDGLFKV DNA damage-binding protein 1 Q16531 (Damage-specific DNA-binding protein 1) 113 QNFVDSKEV DNA excision repair protein ERCC-6 Q03468 114 ALIEKLVEL DNA polymerase alpha subunit B Q14181 (DNA polymerase alpha 70 kDa subunit) 115 VIEDDVNMAIR DNA replication licensing factor P49736 MCM2 (Minichromosome maintenance protein 2 homolog) 116 SQDEIKQEV DNA2-like homolog (EC 3.6.1.-) P51530 (DNA replication ATP-dependent helicase-like homolog) 117 HLNGSCHLLI Estrogen response element binding O77798 protein (cotton-top Tarmarin), 118 ALIDRMVNL DNA2-like homolog (human) P35638 DNA damage-inducible transcript 3 (DDIT-3)(Growth arrest and DNA- damage-inducible protein GADD153) 119 SQKIQEAVKA DNA-directed RNA polymerase I O95602 largest subunit (EC 2.7.7.6) 120 LFDLVEEVQ DnaJ homolog subfamily C member Q96KC8 1 121 LLAALLLDP Splice isoform 2 of P35462 P35462-2 122 FLDESRSTQYM RuvB-like 2 (EC 3.6.1.-)(48-kDa Q9Y230 TATA box-binding protein- interacting protein) 123 VLLGKVYVV DRE1_protein Q9NXT9 124 TIDELKEQV Dynactin-1 (150 kDa dynein- Q14203 associated polypeptide) 125 NLAYENVKE Dynein heavy chain, cytosolic Q14204 (DYHC) 126 SEVEQYVKY Dynein heavy chain, cytosolic Q14204 (DYHC) 127 ETQLTYRR Echinoderm microtubule associated Q6UYC9 protein-like 5 128 IKDDLEDLI ECT2 protein (Epithelial cell- Q9H8V3 transforming sequence 2 oncogene) 129 QVLGKIERA Endothelial differentiation-related 060869 factor 1 (EDF-1) 130 IQINLQRKM Developmentally-regulated O43854 endothelial cell locus 1 protein) 131 KLIEKLDIKL Elongation factor 2 (EF-2) P13639 132 YLNEIKDSV Elongation factor 2 (EF-2) P13639 133 YLAEKYEWDV Elongation factor 2 (EF-2) P13639 134 VFEESQVAGT Elongation factor 2 (EF-2) P13639 135 DAQKEIVRAQK J domain protein C21orf55 Q9NX36 136 DLEETVFTAS J domain protein C21orf55 Q9NX36 137 AMLEGGVDGLL EMILIN-3 precursor (EMILIN-5) Q9NT22 (Elastin microfibril interface-located protein 5) 138 RKADEKRIR Synaptotagmin-like protein 4 Q96C24 (Exophilin-2) 139 ALQEMVHQV Enhancer of filamentation 1 (HEF1) Q14511 140 ILAINKPQNK Enhancer of filamentation 1 (HEF1) Q14511 141 SMYGVDLHHA Band 4.1-like protein 3 (4.1B) Q9Y2J2 (Differentially expressed in adenocarcinoma of the lung protein 1)(DAL-1) 142 SEDITRYYL Band 4.1-like protein 3 (4.1B) Q9Y2J2 (Differentially expressed in adenocarcinoma of the lung protein 1)(DAL-1) 143 NQQEQEDLE Epidermal growth factor receptor P42566 substrate 15 144 SKEEDPFNV Epidermal growth factor receptor P42566 substrate 15 145 FLDKQGFYV Epidermal growth factor receptor P42566 substrate 15 (Protein Eps15)(AF-1p protein) 146 TGALIYAIHA Epithelial membrane protein 3 (EMP- P54852 3)(YMP protein) 147 AVQVLMVLSL Epithelial membrane protein 3 (EMP- P54852 3)(YMP protein) 148 TLKEVEELEQL Zyxin (Zyxin-2) Q15942 149 VLMTEDIKL Eukaryotic translation initiation Q04637 factor 4 gamma 1 150 FEKKQKEMD Eukaryotic translation initiation Q04637 factor 4 gamma 1 151 ELQALYALQAL Eukaryotic translation initiation Q04637 factor 4 gamma 1 152 WSNKYDPPL F-actin capping protein beta subunit P47756 153 NLSDLIDLV F-actin capping protein beta subunit P47756 154 FLSHKLDIK Protocadherin Fat 2 precursor (hFat2) Q9NYQ8 (Multiple epidermal growth factor- like domains 1) 155 VEPALRKPP Protocadherin Fat 2 precursor (hFat2) Q9NYQ8 (Multiple epidermal growth factor- like domains 1) 156 QVVYSLPDSA Protocadherin Fat 2 precursor (hFat2) Q9NYQ8 (Multiple epidermal growth factor- like domains 1) 157 EKISSYQLK Protocadherin Fat 2 precursor (hFat2) Q9NYQ8 (Multiple epidermal growth factor- like domains 1) 158 FMDPQKMPYL KIAA1752 protein Q9C0B1 159 VTNRARASKD Fc alpha/mu receptor Q8WWV6 160 SMNLTISAGP Fc alpha/mu receptor Q8WWV6 161 VTYLQNGKGR Low affinity immunoglobulin gamma P08637 Fc region receptor III-A precursor (IgG Fc receptor 111-2) 162 ELLKTARSSK FYVE, RhoGEF and PH domain- Q7Z6J4 containing protein 2 (Zinc finger FYVE domain-containing protein 4) 163 LKEYIQKLP FYVE, RhoGEF and PH domain- Q7Z6J4 containing protein 2 (Zinc finger FYVE domain-containing protein 4) 164 YLNKLLITR Fibroblast growth factor receptor-like Q8N441 1 precursor (FGF receptor-like protein 1) 165 IARPVGSSVR Fibroblast growth factor receptor-like Q8N441 1 precursor (FGF receptor-like protein 1) 166 QCPVEGDPPPL Fibroblast growth factor receptor-like Q8N441 1 precursor (FGF receptor-like protein 1) 167 TEDNVMKIA Fibroblast growth factor receptor 4 P22455 precursor (EC 2.7.10.1) 168 YLLDVLERS Fibroblast growth factor receptor 4 P22455 precursor (EC 2.7.10.1) 169 TASPDYLEI Fibroblast growth factor receptor 2 P21802 precursor (EC 2.7.10.1)(FGFR-2) 170 TENNVMKIA Fibroblast growth factor receptor 2 P21802 precursor (EC 2.7.10.1)(FGFR-2) 171 ETFKQIDMDND FK506-binding protein 7 precursor Q9Y680 (EC 5.2.1.8) 172 GLLELIEEP Glomulin (FKBP-associated protein) Q92990 (FK506-binding protein-associated protein) 173 FVEEVIDNK Glomulin (FKBP-associated protein) Q92990 (FK506-binding protein-associated protein) 174 LQLYINKLD Glomulin (FKBP-associated protein) Q92990 (FK506-binding protein-associated protein) 175 EQSLETTKV FKSG73 Q9BWW1 176 VFNDELPASI Flavin containing monooxygenase 3 Q53FVV5 isoform 2 variant 177 SLFPGKLEV Protein flightless-1 homolog Q13045 178 QKKLVDTIE Guanylate-binding protein 4 Q96PP9 179 DVGKDQEFTV Filamin-A (Alpha-filamin)(Filamin- P21333 1)(Endothelial actin-binding protein) 180 YLLKDKGEYTL Filamin-A (Alpha-filamin)(Filamin- P21333 1)(Endothelial actin-binding protein) 181 KTTDDIVKV FLJ10101 protein Q8WU94 182 IEQERLER CDNA FLJ14503 fis, clone Q96T17 NT2RM1000252, weakly similar to H. sapiens E-MAP-115 mRNA 183 KINSAPSSPIK E2F8 protein Q5BKY4 184 NNDICLDEV Human Hypothetical protein Q2VPJ3 185 VFAEVGCSPC HUMAN CDNA FLJ34154 fis, clone Q8NB70 FCBBF3013058 186 NIVETVLDL Hypothetical protein FLJ43654 Q6ZUJ4 (Hypothetical protein C3orf62) 187 IYIDGVQEVF HUMAN CDNA FLJ46180 fis, clone Q6ZRQ5 TESTI4004031 188 KIMTEKELLAV Flotillin-2 (Epidermal surface Q14254 antigen)(ESA) 189 VEAQEILR Flotillin-2 (Epidermal surface Q14254 antigen)(ESA) 190 MLLDFIQHI Serine/threonine-protein kinase ATR Q13535 (EC 2.7.11.1)(Ataxia telangiectasia and Rad3-related protein)(FRAP- related protein 1) 191 SLLESVQKL Serine/threonine-protein kinase ATR Q13535 (EC 2.7.11.1)(Ataxia telangiectasia and Rad3-related protein)(FRAP- related protein 1) 192 YLQPKLLGI Serine/threonine-protein kinase ATR Q13535 (EC 2.7.11.1)(Ataxia telangiectasia and Rad3-related protein)(FRAP- related protein 1) 193 YLLVGTLFLL Frizzled 5 precursor (Frizzled-5) Q13467 194 MAAGDYPEA Frizzled 5 precursor (Frizzled-5) Q13467 195 LYLLVGTLFL Frizzled 5 precursor (Frizzled-5) Q13467 196 ALSDHHVYL Fructose-bisphosphate aldolase C P09972 (EC 4.1.2.13) 197 YLAPHVRTL G protein pathway suppressor 1 Q53HS2 isoform 1 variant 198 YLQNWSHVL G protein pathway suppressor 1 Q53HS2 isoform 1 variant 199 FAALMLLGLV KiSS-1 receptor (KiSS-1R) Q969F8 (Kisspeptins receptor)(Metastin receptor)(G-protein coupled receptor 54) 200 MINLAVFDL Probable G-protein coupled receptor Q9Y2T6 55 201 EASALAVAPSAK Probable G-protein5 coupled receptor Q9HC97 35 202 TFVLTIILV G-protein coupled receptor family C Q9NQ84 group 5 member C precursor (Retinoic acid-induced gene 3 protein) 203 FLLDFEEDL Leucine-rich repeat-containing G- O75473 protein coupled receptor 5 precursor (Orphan G-protein coupled receptor HG38)(G-protein coupled receptor 49)(G-protein coupled receptor 67) 204 FAMDSYGTSN Probable G-protein coupled receptor Q6QNK2 133 precursor (G-protein coupled receptor PGR25) 205 MELSEPIVEN G1 to S phase transition protein 1 P15170 homolog (GTP-binding protein GST1-HS) 206 WLENALGKL Gamma-aminobutyric-acid receptor Q16445 alpha-6 subunit precursor (GABA(A) receptor) 207 KILEHDDVSYL Ganglioside-induced differentiation- Q96MZ0 associated protein 1-like 1 (GDAP1- L1) 208 SQQNTDNLV Gap junction alpha-5 protein P36382 (Connexin-40)(Cx40) 209 SKLCEETPI GEM-interacting protein (GMIP) Q9P107 210 QLVVELKDI Golgin subfamily B member 1 Q14789 (Giantin) 211 VFDIFQFAK UDP-N-acetylhexosamine Q16222 pyrophosphorylase (Antigen X) 212 NIANHFFTV UDP-N-acetylhexosamine Q16222 pyrophosphorylase (Antigen X) 213 HLIHEVTKV Neutral alpha-glucosidase AB Q14697 precursor (EC 3.2.1.84) 214 FLDPNNIPKA Probable dolichyl pyrophosphate Q9BVK2 Glc1Man9G1cNAc2 alpha-1,3- glucosyltransferase (EC 2.4.1.-) 215 KINEAVECLLSL Bifunctional aminoacyl-tRNA P07814 synthetase [Includes: Glutamyl-tRNA synthetase (EC 6.1.1.17)(Glutamate- -tRNA ligase); Prolyl-tRNA synthetase (EC 6.1.1.15)(Proline-- tRNA ligase)] 216 LLQTPKLLL Glycoprotein nmb-like protein Q8IXJ5 217 VLLYSVVVV Prolactin-releasing peptide receptor P49683 (PrRP receptor)(PrRPR)(G-protein coupled receptor 10) 218 KFKQCKLLQ G protein-coupled receptor 112 Q5EGP2 219 DVLSTSSAISL G protein-coupled receptor 112 Q5EGP2 220 YIDDHSWTL Growth factor receptor-bound protein Q14449 14 (GRB14 adapter protein) 221 SLYEENNKL GRIP and coiled-coil domain- Q8IWJ2 containing protein 2 (Golgi coiled coil protein GCC185)(CTCL tumor antigen se1-1) 222 KLLEVQILE GRIP and coiled-coil domain- Q8IWJ2 containing protein 2 (Golgi coiled coil protein GCC185)(CTCL tumor antigen se1-1) 223 KPLLEQKEL GRIP and coiled-coil domain- Q8IWJ2 containing protein 2 (Golgi coiled coil protein GCC185)(CTCL tumor antigen se1-1) 224 FPWELDPDWS GROS1-L protein Q9HC86 225 YLSAAINPIL Growth hormone secretagogue Q92847 receptor type 1 (GHS-R) 226 QLSLADVILL Glutathione S-transferase A4-4 (EC O15217 2.5.1.18) 227 QSFLVGNQL Glutathione S-transferase A4-4 (EC O15217 2.5.1.18) 228 LKNKTKEAAE GTP-binding protein Rhes (Ras Q96D21 homolog enriched in striatum) (Tumor endothelial marker 2) 229 EDFHRKVYNI GTP-binding protein Rhes (Ras Q96D21 homolog enriched in striatum) (Tumor endothelial marker 2) 230 YIDDVFHAL GTP-binding protein Rit1 (Ras-like Q92963 protein expressed in many tissues) 231 EQLAELRQEF VGFG2573 Q6UY45 232 GLLERVKEL Hypothetical protein HDLBP Q53QU2 233 DAILRIVGE Hypothetical protein HDLBP Q53QU2 234 RHKLVSDGQ Heat shock protein 75 kDa, Q12931 mitochondrial precursor (HSP 75) (Tumor necrosis factor type 1 receptor-associated protein) 235 IQLVMKVIE Heat shock protein apg-1 Q53ZP9 236 MTREELVKN Tumor rejection antigen (Gp96) 1 Q5CAQ5 237 ALKDKIEKA Tumor rejection antigen (Gp96) 1 Q5CAQ5 238 KIILRHLIE Heat-shock protein beta-3 (HspB3) Q12988 (Heat shock 17 kDa protein) 239 TLGKLFWV Low-density lipoprotein receptor- O75197 related protein 5 precursor 240 KGQGGAGGQFL Regulator of telomere elongation Q9NZ71 helicase 1 (EC 3.6.1.-)(Helicase-like protein NHL) 241 KEFLVVASV Hematopoietic protein 1 Q52LW0 242 KIAQKALDL Heme oxygenase 1 (EC 1.14.99.3) P09601 (HO-1) 243 ITEPLPELQL Heparan sulfate glucosamine 3-O- Q8IZT8 sulfotransferase 5 (EC 2.8.2.23) 244 KLRKEKEEF Hepatocellular carcinoma-associated Q9NYH9 antigen 66 245 EDVFPNILN Melanoma-associated antigen E2 Q8TD90 (MAGE-E2 antigen)(Hepatocellular carcinoma-associated protein 3) 246 IAVMLLEGGAN 26S proteasome non-ATPase O75832 regulatory subunit 10 (26S proteasome regulatory subunit p28) 247 VDLFPGTFEV Hepatocellular carcinoma-associated Q5JUU1 protein p28-II Hephaestin 248 MVCGSPDIPL HECT domain and RCC1-like O95714 domain-containing protein 2 (HERC2) 249 DAPHSEGDMHLL HECT domain and RCC1-like O95714 domain-containing protein 2 (HERC2) 250 DTIEIITDR Heterogeneous nuclear P22626 ribonucleoproteins A2/B1 (hnRNP A2/hnRNP B1) 251 RLFVGSIPK Heterogeneous nuclear O43390 ribonucleoprotein R (hnRNP R) 252 FLSEYQHQP HEXIM1 protein (HMBA-inducible) O94992 253 LALMISMISAD Histatin-1 precursor (Histidine-rich Histatin-1 protein 1) precursor (Histidine-rich protein 1) 254 RMLPHAPGV Histone deacetylase 1 (HD1) Q13547 255 THNLLLNYGL Histone deacetylase 1 (HD1) Q13547 256 SPNMNAVISL Histone deacetylase 9 (HD9)(HD7B) Q9UKV0 (HD7) 257 EFIDLLKKM Homeodomain-interacting protein Q9H2X6 kinase 2 (EC 2.7.11.1) 258 KMINHDSEKED Cullin-2 (CUL-2) Q13617 259 AVDEDRKMYL Cullin-2 (CUL-2) Q13617 260 LFELLEKEI SWI/SNF-related matrix-associated O60264 actin-dependent regulator of chromatin subfamily A member 5 (EC 3.6.1.-) 261 FISEFEHRV HUMAN HSPC027 26S proteasome Q9Y6E3 non-ATPase regulatory subunit 13 Synonyms 26S proteasome regulatory subunit S 11 26S proteasome regulatory subunit p40.5 262 AMFDHIPVGV Hypothetical protein (Novel protein Q9Y3I0 HSPC117)(DJ149A16.6 protein) (Hypothetical protein HSPC117) 263 WSFCLACV Claudin domain-containing protein 1 Q9NY35 (Membrane protein GENX-3745) Q9NY35 264 NLLFPIIYL Large neutral amino acids transporter Q9UHI5 small subunit 2 (L-type amino acid transporter 2)(hLAT2) 265 SLLENLEKI Heterogeneous nuclear O60812 ribonucleoprotein C-like 1 (hnRNP core protein C-like 1) 266 ILDQKINEV Ornithine decarboxylase (EC P11926 4.1.1.17)(ODC) 267 DQINIETKN Regulator of nonsense transcripts 2 Q9HAU5 (Nonsense mRNA reducing factor 2) (Up-frameshift suppressor 2 homolog)(hUpf2) 268 PFQNLLKEY Regulator of nonsense transcripts 2 Q9HAU5 (Nonsense mRNA reducing factor 2) (Up-frameshift suppressor 2 homolog)(hUpf2) 269 LELELENLEI Regulator of nonsense transcripts 2 Q9HAU5 (Nonsense mRNA reducing factor 2) (Up-frameshift suppressor 2 homolog)(hUpf2) 270 GLADASLLKKV ATX10_HUMAN Ataxin-10 Q9UBB4 271 GQILEAAVSV KIAA1833 protein Q569G6 272 RVVSVSFRV HUMAN UDP-GalNAc: betaGlcNAc Q8NCR0 beta 1,3-galactosaminyltransferase, polypeptide 2 (Beta 1,3-N- acetylgalactosaminyltransferase-II) (MGC39558) 273 TQKRLDVYL Hypothetical protein KIAA1033 Q2M389 274 AMLTVLHEI Activating signal cointegrator 1 Q8N3C0 complex subunit 3 (EC 3.6.1.-) 275 ARLAALVQR Delta-interacting protein A (Hepatitis Q15834 delta antigen-interacting protein A) (Coiled-coil domain-containing protein 85B) 276 FAVHFYRS Hypothetical protein FLJ14466 Q96BP7 Interferon-inducible double stranded 277 FNITYLDID RNA-dependent protein kinase O75569 activator A 278 GLAKRVWSL Hypothetical protein C9orf142 Q9BUH6 279 HLDATKLLL Tetratricopeptide repeat protein 17 Q96AE7 280 IGSFHGVLSL CDNA FLJ14058 fis, clone Q9H7Z0 HEMBB1000554 281 ILDLIDDAW Anaphase promoting complex Q9BS18 subunit 13 282 KLLEMVRED Hypothetical protein CCDC60 Q8IWA6 283 LSYLPATVEP Sphingosine kinase 2 (EC 2.7.1.-) Q9NRA0 284 QLAQFVHEV Probable ATP-dependent RNA Q96FC9 helicase DDX11 (EC 3.6.1.-) (DEAD/H box protein 11)(CHL1 homolog)(Keratinocyte growth factor-regulated gene 2 protein) (KRG-2) 285 SYDESDEEE Protein KIAA0182 Q14687 286 SYSDEFGPS Ras GTPase-activating protein Q96PV0 SynGAP (Synaptic Ras-GTPase- activating protein 1)(Synaptic Ras- GAP 1)(Neuronal RasGAP) 287 TVERADSSHLSI Fibrinogen C domain containing 1 Q8N539 288 VTENELAVIT MGC39581 protein Q86XM0 289 VTYLEDYSA Bcl-2-like 13 protein (Mill protein) Q9BXK5 (Bcl-rambo) 290 YLLEKTRVA Myosin head domain containing 1 Q96H55 291 TLKILDLME WD-repeat protein 51A Q8NBT0 292 EDLIKELIK KIF27A (OTTHUMP00000021559) Q86VH2 293 LSLENLEKI Inositol polyphosphate-5-phosphatase Q2T9J4 F, isoform 1 294 FLNKAADFIE Myopalladin Q96KF5 295 GLDIDGIYRV Rho GTPase activating protein 12 Q5T2Y2 296 QNNNLQTQI Hypothetical protein Q7Z3C5 DKFZp686D0630 297 FLDDVVHSL Jumonji domain-containing protein Q15652 1C (Thyroid receptor-interacting protein 8)(TRIP-8) 298 NMVDLNDY Coatomer subunit beta (Beta-coat P53618 protein)(Beta-COP) 299 YLLKEDMAGI FLJ10462 fis, clone NT2RP1001494, Q9NVW8 weakly similar to MALE STERILITY PROTEIN 2 300 KLFEKVKEV FLJ10462 fis, clone NT2RP1001494, Q9NVW8 weakly similar to MALE STERILITY PROTEIN 2 301 TVMDEIHTV Cell-cycle and apoptosis regulatory Q6X935 protein 1 302 KLISELQKL Telomere-associated protein RIF1 Q5UIP0 (Rap1-interacting factor 1 homolog) 303 KVIDEIYRV F-box only protein 28 Q9NVF7 304 SSLSDGLLLE CDNA F1110901 fis, clone Q9NV65 NT2RP5003524 305 EEIVKVTFE Acetoacetyl-CoA synthetase (EC Q86V21 6.2.1.16) 306 ELLENIIKN Putative cell cycle control protein Q9NXZ0 (DEP domain containing 1) 307 ELLSLVQNL Synaptopodin 2-like Q68A20 308 PQQERDFY CDNA FLJ36560 fis, clone Q8N9T8 TRACH2009340 309 GRGGKDPPLEP CDNA FLJ13330 fis, clone Q9H8Q0 OVARC1001802 310 LADISLHDPV ATP-dependent RNA helicase Q9H8H2 DDX31 (EC 3.6.1.-)(DEAD box protein 31)(Helicain) 311 PSNMGIAIPL Protein C14orf161 Q9H7T0 312 FMMPQSLGV Cysteine protease ATG4B (EC Q9Y4P1 3.4.22.-)(Autophagy-related protein 4 homolog B) 313 IMVATAVVAI CDNA FLJ14526 fis, clone Q96T08 NT2RM1001139 314 MTKRYEALE Hypothetical protein CCDC77 Q9BR77 (CDNA FLJ14732 fis, clone NT2RP3001969, weakly similar to TRICHOHYALIN) 315 SLDAKEIYL CDNA FLJ14790 fis, clone Q96K38 NT2RP4000973, weakly similar to PROBABLE PROTEIN DISULFIDE ISOMERASE P5 (EC 5.3.4.1) 316 QLLDIKTRL Keratin 24 Q2M2I5 317 FLTDYLNDL BCoR protein (BCL-6 corepressor) Q6W2J9 318 ANQGGFENGE Hypothetical protein FLJ20582 Q6IQ21 319 ILGLLLLHLE Hypothetical protein FLJ22688 Q9BT04 320 VYQKEGVLAS Hypothetical protein FLJ22944 Q9H5W3 321 YLNDFTHEI Zinc finger protein, subfamily 1A, 5- Q8TBE5 322 SPPLQGEIS Leucine-rich repeats and IQ motif Q8IW35 containing 2 323 LFFEPVTTP Hypothetical protein FLJ23749 Q8TEA0 324 WISVPVVT Hypothetical protein FLJ25336 http://www. expasy.org/ sprot/userman. html-AC line Q96LP1 325 NMEIMPEGSL Hypothetical protein FLJ25660 Q8N7G6 CDNA FLJ30058 fis, clone 326 QDQLSALQL ADRGL2000074, weakly similar to Q96NU6 RHO-GTPASE-ACTIVATING PROTEIN 6 327 MEADPDLSR CDNA FLJ30106 fis, clone Q96A82 BNGH41000190, weakly similar to Rattus norvegicus schlafen-4 (SLFN- 4) mRNA. 328 LYLPATTPY Whirlin Q9P202 329 SEIEKNKKV CDNA FLJ31846 fis, clone Q96MV0 NT2RP7000425, weakly similar to MYOSIN HEAVY CHAIN, NONMUSCLE TYPE B 330 SLVQIVTTL FLJ32833 fis, clone TESTI2003228 Q96M43 331 KILDIRKNV Guanine nucleotide-binding protein P38405 G(olf), alpha subunit (Adenylate cyclase-stimulating G alpha protein, olfactory type) 332 QSLELLLLPV CDNA FLJ33811 fis, clone Q8N279 CTONG2002095 333 ALLNNIIEI Transmembrane protein 16C Q9BYT9 334 FNQSSSLIIH Zinc finger protein 31 (Zinc finger P17040 protein KOX29)(Zinc finger and SCAN domain-containing protein 20) (Zinc finger protein 360) 335 LSLSALPVSY Transmembrane 6 superfamily Q9BZW4 member 2 336 YLDLTPNQE CDNA FLJ90251 fis, clone Q8NCH3 NT2RM4000115 337 YLFERIKEL CDNA FLJ90251 fis, clone Q8NCH3 NT2RM4000115 338 FILDVLLPEA CDNA FLJ90760 fis, clone Q8N2I4 THYRO1000061 339 EFIPEFEK Tubulin--tyrosine 12 ligase-like protein Q14166 12 340 DVFPATPGSQN KIAA0303 protein O15021 341 FIFDVHVHEV Plexin-B2 precursor (MM1) O15031 342 ILEVTNNLE Zinc finger and BTB domain- O15062 containing protein 5 343 ILSKKDLPL Centrosome-associated protein 350 Q8WY20 344 HEPPKAVDK piccolo (Aczonin) Q9Y6V0 345 ILDDSHLLV KIAA0560 protein O60306 346 YLDNVVNKQ KIAA0676 protein Q96H49 347 KLLPYVGLLQ Human homolog of Mus SLIT and Q810B7 NTRK-like protein 5 precursor 348 QLKSLIQID Human homolog of Mus SLIT and Q810B7 NTRK-like protein 5 precursor 349 SLLNNPLSI Nischarin Q6PIB4 350 SSLSDALVLE FERM domain-containing protein 4A Q9P2Q2 351 DELQQLFNL Leucine-rich repeats neuronal protein Q6UXK5 1 precursor (Neuronal leucine-rich repeat protein 1)(NLRR-1) 352 QILSGRKPEL KIAA1512 protein Q9P216 353 KLVEVIEEV KIAA1598 protein Q9HCH4 354 QTLLKNPLY hosphatidylinositol-3 phosphate 3- Q96QU2 phosphatase adaptor subunit 355 SLLDDLHSA KIAA1730 protein Q9C0D3 356 HILDSSIYS KIAA1786 protein Q96JN9 357 QSSPPPPPPS Hypothetical protein MGC20470 Q96EK3 358 LMCYAIMVT OACT1 protein Q86XC2 359 FLSEEGGHVAV 6-phosphofructo-2-kinase/fructose- Q16877 2,6-biphosphatase 4 (6PF-2-K/Fru- 2,6-P2ASE testis-type isozyme) 360 SPDQELVLL IkappaB kinase complex-associated O95163 protein (IKK complex-associated protein)(p150) 361 FLLVVLLKL Immune receptor expressed on Q7Z7I3 myeloid cells 2 362 QIIEANYHS High-affinity cAMP-specific and O60658 IBMX-insensitive 3′,5′-cyclic phosphodiesterase 8A (EC 3.1.4.17) 363 ILIDKSGKLEL Bone specific CMF608 Q6WRI0 364 TVMDSKIVQV Importin alpha-7 subunit O60684 (Karyopherin alpha-6) 365 VMDSKIVQV Importin alpha-7 subunit O60684 (Karyopherin alpha-6) 366 YQDPLDPTRSV InaD-like protein (Inadl protein) Q8NI35 (hINADL)(Pals1-associated tight junction protein)(Protein associated to tight junctions) 367 HEFLTPRL InaD-like protein (Inadl protein) Q8NI35 (hINADL)(Pals1-associated tight junction protein)(Protein associated to tight junctions) 368 GLFPWTPKL InaD-like protein (Inadl protein) Q8NI35 (hINADL)(Pals1-associated tight junction protein)(Protein associated to tight junctions) 369 CDVQRYNI Nitric oxide synthase, inducible (EC P35228 1.14.13.39) 370 NMYGKVVTV Transcription elongation factor SPT5 O00267 (hSPT5) 371 QNVQVNQKV Inositol-trisphosphate 3-kinase B (EC P27987 2.7.1.127)(Inositol 1,4,5- trisphosphate 3-kinase B) 372 SLINQMTQV Type I inositol-3,4-bisphosphate 4- Q96PE3 phosphatase (EC 3.1.3.66)(Inositol polyphosphate 4-phosphatase type I) 373 NVTVAVPTV Insulin receptor beta subunit Q9UCB7 374 LGLENLCHL Insulin-like growth factor binding Q8TAY0 protein, acid labile subunit 375 YYEKLHTYF Integrin beta-4 precursor (GP150) P16144 (CD104 antigen) 376 LLAALLLDP Splice isoform 2 of P35462 P35462-2 377 RRDFGFPQ Interferon alpha 2 protein Q16055 378 SLLGFVYKL Interferon-induced protein with P09914 tetratricopeptide repeats 1 (IFIT-1)) (Interferon-induced 56 kDa protein) (IFI-56K) 379 LDRVFKNY Interleukin-20 precursor (IL-20) Q9NYY1 (Four alpha helix cytokine Zcyto10) 380 LMVDHVTEV Steroid receptor RNA activator Q9HD15 isoform 1 381 KMDQQEFSI Intersectin-2 (SH3 domain- Q9NZM3 protein 1B)(SH3P18) (SH3P18-like WASP-associated protein) 382 SLLLLPEEL ITI-like protein (Inter-alpha Q6UXX5 (Globulin) inhibitor H5-like) 383 SQQNTDNLV Gap junction alpha-5 protein P36382 (Connexin-40) 384 WLDETLAQV Kelch-like protein 8 Q9P2G9 385 VNLGGSKSISIS Keratin, type II cytoskeletal 1 P04264 (Cytokeratin-1) 386 ANYLDSMYI ADAM 9 precursor (EC 3.4.24.-)(A Q13443 disintegrin and metalloproteinase domain 9) (Metalloprotease/disintegrin/cysteine- rich protein 9)(Myeloma cell metalloproteinase) 387 HLWNSIHGL Next to BRCA1 gene 1 protein Q14596 (Neighbor of BRCA1 gene 1 protein) (Membrane component, chromosome 17, surface marker 2)(1A1-3B) 388 SLADLMPRV Hypothetical protein Q6MZZ8 DKFZp686K2075 389 IDLSASLVLN KIAA0100 protein Q14667 390 HLTYLNVYL Pre-mRNA-splicing factor ATP- Q92620 dependent RNA helicase PRP16 (EC 3.6.1.-)(ATP-dependent RNA helicase DHX38)(DEAH box protein 38) 391 QLVACIESKL KIAA0251 protein Q8TBS5 392 EGKLVVQDIE HUMAN KIAA0342 protein O15050 393 QALEAGAVVLI KIAA0357 protein O15064 394 VLSCSQALKI Hypothetical protein KIAA0372 Q6PGP7 395 LSIEGEQEL KIAA0377 splice variant 2 Q86TE7 396 EFQDLNQEV KIAA0386 protein Q9Y4F9 397 RTKLTDIQI HUMAN CTCL tumor antigen HD- Q548S1 CL-04 398 RECKYDLPP Importin-13 (Imp13)(Ran-binding O94829 protein 13) 399 QLTKIQTEL KIAA0769 protein O94868 400 LVNAAQSVFV Hypothetical protein KIAA0863 Q6IQ32 401 VKAEDKARV Zinc finger protein KIAA1196- Q96KM6 402 VLHDRIVSV CRSP complex subunit 3 (Cofactor Q9ULK4 required for Sp1 transcriptional activation subunit 3)(Transcriptional coactivator CRSP130)(Vitamin D3 receptor-interacting protein complex 130 kDa component 403 RNSIATLQGGR [Pyruvate dehydrogenase Q9P2J9 [lipoamide]] phosphatase2, mitochondrial precursor (EC 3.1.3.43) 404 TVNILIVDQN Protocadherin-10 precursor Q9P2E7 405 YLFDLPLKV Leucine-rich repeats and calponin Q5VUJ6 homology (CH) domain containing 2 406 NLAKDNEVL Ankyrin repeat domain 18B Q5W0G2 407 SGDKLKLDQT Kin17 protein (HsKin17 protein) O60870 (KIN, antigenic determinant of recA protein homolog) 408 KLTDYQVTL Kinesin-like protein KIF13A Q9H1H9 (Kinesin-like protein RBKIN) 409 KIQEILTQV Putative RNA binding protein KOC O00425 410 YLDEQIKKV HUMAN Kinesin-like protein Q9H1H9 KIF13A (Kinesin-like protein RBKIN) 411 SSIVVEVDSLH HUMAN Kinesin-like protein Q9H1H9 KIF13A (Kinesin-like protein RBKIN) 412 RLASYLDRV Keratin, type I cytoskeletal 18 P05783 (Cytokeratin-18) 413 ALLNIKVKL Keratin, type I cytoskeletal 18 P05783 (Cytokeratin-18) 414 FNIVKNKTE Kv3.2d voltage-gated potassium Q86W09 channel 415 KAITAPVSL Lethal(3)malignant brain tumor-like Q9Y468 protein (L(3)mbt-like)(L(3)mbt protein homolog) 416 HEYLKAFKV Lactadherin precursor (Milk fat Q08431 globule-EGF factor 8)(MFG-E8) (HMFG)(Breast epithelial antigen BA46)(MFGM) 417 LKAFKVAYS Lactadherin precursor (Milk fat Q08431 globule-EGF factor 8)(MFG-E8) (HMFG)(Breast epithelial antigen BA46)(MFGM) 418 RLAVYIDRV Lamin-A/C (70 kDa lamin) P02545 419 YLLGNSSPRT Lamin-A/C (70 kDa lamin) P02545 420 EMKVSDLDR Laminin gamma-1 chain precursor P11047 (Laminin B2 chain) 421 VRLVDAGGVKL Low-density lipoprotein receptor- O75197 related protein 5 precursor 422 KPETFEHLF Leptin receptor precursor (LEP-R) P48357 (OB receptor) 423 EITDDGNLK Leptin receptor precursor (LEP-R) P48357 (OB receptor) 424 ECHHRYAEL Leptin receptor precursor (LEP-R) P48357 (OB receptor) 425 PSTCPDGFKI Mitogen-activated protein kinase O43283 kinase kinase 13 (EC 2.7.11.25) 426 RKGIIDVNL Leukemia virus receptor 2 Q08357 427 LIQERDVKK Leukemia-associated protein with a Q8NFU7 CXXC domain 428 LTLEQVVAIE Leukemia-associated protein with a Q8NFU7 CXXC domain 429 RDTPHSDFRG RNA-binding protein 6 (RNA- P78332 binding motif protein 6)(RNA- binding protein DEF-3)(Lung cancer antigen NY-LU-12) 430 HRVLLHLF Lung cancer oncogene 5 Q7Z5Q7 431 LLFDRPMHV Heterogeneous nuclear P52272 ribonucleoprotein M (hnRNP M) 432 FLSELTQQL Macrophage migration inhibitory P14174 factor (MIF)(Phenylpyruvate tautomerase)(EC 5.3.2.1) 433 SLLSHVEQL Mitotic spindle assembly checkpoint Q9UI95 protein MAD2B (MAD2-like 2) (hREV7) 434 KLILRLHKL Mitogen-activated protein kinase Q9Y6R4 kinase kinase 4 (EC 2.7.11.25) (MAPK/ERK kinase kinase 4) 435 RLTHHPVYI Serine/threonine/tyrosine-interacting- Q9Y6J8 like protein 1 (Dual-specificity protein phosphatase 24)(Map kinase phosphatase-like protein MK-STYX) 436 QDNLEKLLQ Microtubule-associated Q6P0Q8 serine/threonine-protein kinase 2 (EC 2.7.11.1) 437 MKRLLLLF Matrix metalloprotease MMP-27 Q9H306 438 DPQDILEVK MCM10 protein Q7L590 439 FLFGEVHKA MCM10 protein Q7L590 440 KVIVLVNKVLL Interferon-induced helicase C Q9BYX4 domain containing protein 1 (EC 3.6.1.-)(Melanoma differentiation- associated protein 5) 441 QILSLEEKI Melanoma ubiquitous mutated Q2TAK8 protein 442 MLKDIIKEY Melanoma antigen family D, 2 Q5BJF3 443 KTWGQYWQV Melanocyte protein Pmel 17 P40967 precursor (Melanocyte lineage- specific antigen GP100) 444 LLDGTATLRL Melanocyte protein Pmel 17 P40967 precursor (Melanocyte lineage- specific antigen GP100) 445 VLKEIVERV GPI-anchored protein p137 Q14444 (p137GPI)(Membrane component chromosome 11 surface marker 1) Cytoplasmic activation/proliferation- associated protein 1 446 SLLDEFYKL GPI-anchored protein p137 Q14444 (p137GPI)(Membrane component chromosome 11 surface marker 1) Cytoplasmic activation/proliferation- associated protein 1 447 TLNQNGYTLV Hepatocyte growth factor receptor P08581 precursor (EC 2.7.10.1)(HGF receptor)(Scatter factor receptor)(SF receptor)(HGF/SF receptor)(Met proto-oncogene tyrosine kinase) 448 QMPKMNFAN Mitogen-activated protein kinase 14 Q16539 (EC 2.7.11.24) 449 KLADFGVSGE Mitogen-activated protein kinase Q12851 kinase kinase kinase 2 (EC 2.7.11.1) (MAPK/ERK kinase kinase kinase 2) 450 SIKDYEQAN Mitotic kinesin-related protein Q96Q89 451 EDLMEDEDL Mitotic kinesin-related protein Q96Q89 452 VLISKELISL Sperm-associated antigen 5 (Astrin) Q96R06 (Mitotic spindle-associated protein p126) 453 LIEKVQEAR Myeloid/lymphoid or mixed-lineage Q9UMN6 leukemia protein 4 (Trithorax homolog 2) 454 SRVRMKTPT Myeloid/lymphoid or mixed-lineage Q9UMN6 leukemia protein 4 (Trithorax homolog 2) 455 GLDDIKDLKV Putative helicase MOV-10 (EC Q9HCE1 3.6.1.-)(Moloney leukemia virus 10 protein) 456 VLAETLTQV MOZ/CBP protein Q712H6 457 DTNADKQLS Calgranulin B (Migration inhibitory P06702 factor-related protein 14)(MRP-14) (P14) 458 GRWVCKDLPCP MUC2_HUMAN Mucin-2 precursor Q02817 (Intestinal mucin 2) 459 FGNMQKINQ MUC2_HUMAN Mucin-2 precursor Q02817 (Intestinal mucin 2) 460 FPNWTLAQV Mucin-5B precursor (Mucin 5 Q9HC84 subtype B, tracheobronchial) 461 ATPSSTPETV Mucin-5B precursor (Mucin 5 Q9HC84 subtype B, tracheobronchial) 462 FVNDVNLEN Multiple PDZ domain protein (Multi O75970 PDZ domain protein 1)(Multi-PDZ- domain protein 1) 463 SENKLILMK RUFY2 (Run and FYVE domain- Q8IW33 containing protein Rabip4 464 TFCVQPGEKV Multidrug resistance associated Q8NHX7 protein 7 465 YLNDGLWHM Multiple copies in a T-cell Q9ULC4 malignancies (Malignant T cell amplified sequence 1)(MCT1) 466 GTTLRNLEI DNA mismatch repair protein Msh3 P20585 467 SPPTLNGAPSP Protein CBFA2T2 (MTG8-like O43439 protein)(MTG8-related protein 1) (Myeloid translocation-related protein 1) 468 NEAAIKNVYL Myomesin-1 (190 kDa titin- P52179 associated protein)(190 kDa connectin-associated protein 469 FIDFGMDLQ Myosin heavy chain, cardiac muscle P12883 beta isoform (MyHC-beta) 470 LLEAKVKEL Myosin-13 (Myosin heavy chain, Q9UKX3 skeletal muscle, extraocular)(MyHC- eo) 471 LLAEKVEQL Tumor suppressor candidate 3 (N33 Q13454 protein) 472 LANARGLGLQ Nebulin-related anchoring protein Q8TCH0 473 VNRIGQESLE Neural cell adhesion molecule 1, 1 P13592 474 YLEIQGITR Neurotrimin precursor Q9P121 475 EALENNKEL Ninein Q8N4C6 476 NSMVVERQQL Ninein Q8N4C6 477 HLLERVDQV Ninein Q8N4C6 478 PERTQLLYL Notch homolog 2 Q5VTD0 479 NGGTCEDGIN Neurogenic locus notch homolog P46531 protein 1 precursor (Notch 1)(hN1) (Translocation-associated notch protein TAN-1)[Contains: Notch 1 extracellular truncation; Notch 1 intracellular domain] 480 QSAADYLGAL Neurogenic locus notch homolog Q9UM47 protein 3 precursor (Notch 3) [Contains: Notch 3 extracellular truncation; Notch 3 intracellular domain] 481 ALLVVLSPPAL Neurogenic locus notch homolog Q99466 protein 4 precursor (Notch 4) (hNotch4)[Contains: Notch 4 extracellular truncation; Notch 4 intracellular domain]- 482 LRLDXLFKL Plexin-A1 precursor (Semaphorin Q9UIW2 receptor NOV) 483 WLIEDGKVV HUMAN NPD011 Q9H2R7 484 SQPQEPENK Nuclear autoantigen Sp-100 P23497 (Speckled 100 kDa)(Nuclear dot- associated Sp100 protein) 485 LLREKVEFL Nuclear factor erythroid 2-related Q14494 factor 1 (NF-E2-related factor 1) (NFE2-related factor 1)(Nuclear factor, erythroid derived 2, like 1) (Transcription factor 11) (Transcription factor HBZ17) (Transcription factor LCR-F1) (Locus control region-factor 1) 486 YLDDVNEII Nuclear factor of activated T-cells, O95644 cytoplasmic 1 (NFAT transcription complex cytosolic component)(NF- ATc1) 487 ALLDQLYLA Nuclear receptor coactivator 2 Q15596 (NCoA-2)(Transcriptional intermediary factor 2) 488 TLFDYEVRL Ubiquitin-like PHD and RING finger Q96T88 domain-containing protein 1 (EC 6.3.2.-) 489 SILKVVINN Nucleic acid helicase DDXx Q8IWW2 490 LLYGGDLHSA Nucleic acid helicase DDXx Q8IWW2 491 KLAENIDAQL Nucleoporin 62 kDa (NUP62 protein) Q6GTM2 492 SLLTDEEDVD Nuclear pore complex protein P52948 Nup98-Nup96 precursor [Contains: Nuclear pore complex protein Nup98 (Nucleoporin Nup98)(98 kDa nucleoporin); 493 VDITQEPVL Nuclear pore complex protein P52948 Nup98-Nup96 precursor [Contains: Nuclear pore complex protein Nup98 (Nucleoporin Nup98)(98 kDa nucleoporin); 494 QLEKKLME Nucleoprotein TPR P12270 495 GLDPLGYEIQ Nuclear pore complex protein P57740 Nup107 496 ALLDRIVSV Nuclear pore complex protein Q92621 Nup205 497 KILDLETQL ODF2 protein Q6PJQ8 498 VTWLKETEV Trophoblast glycoprotein precursor Q6PJQ8 (5T4 oncofetal trophoblast glycoprotein) 499 VDLPGVINTV Dynamin-like 120 kDa protein, O60313 mitochondrial precursor (Optic atrophy 1 gene protein) 500 TITCLPATLV Orexin receptor type 2 (Ox2r) O43614 (Hypocretin receptor type 2) 501 LLGPRLVLA Transmembrane emp24 domain- P49755 containing protein 10 precursor (Transmembrane protein Tmp21) 502 LTTPDAAGVNQ Orphan nuclear receptor TR2 P13056 (Testicular receptor 2) 503 FLDGHDLQL MKL/myocardin-like protein 1 Q969V6 (Myocardia-related transcription factor A)(MRTF-A) (Megakaryoblastic leukemia 1 protein)(Megacaryocytic acute leukemia protein) 504 KTTEVLDASA Ovarian cancer related tumor marker Q8WXI7 CA125- 505 TSPTVPWTTSIF Ovarian cancer related tumor marker Q8WXI7 CA125- 506 WTITDTTEH Ovarian cancer related tumor marker Q8WXI7 CA125- 507 TITNLQYGE Ovarian cancer related tumor marker Q8WXI7 CA125- 508 ARLTFLNRG Oxysterol-binding protein-related Q9BZF1 protein 8 (OSBP-related protein 8) 509 KIDALSSEKL Centrosomal protein of 70 kDa Q8NHQ1 (Cep70 protein)(p10-binding protein) 510 LLAEAVLTYL Leucine carboxyl methyltransferase 2 O60294 (EC 2.1.1.-)(p21WAF1/CIP1 promoter-interacting protein) 511 SLFEKGLKNV F-box/LRR-repeat protein 5 (F-box Q9UKA1 and leucine-rich repeat protein 5)(F- box protein FBL4/FBLS) 512 LDTPSQPVNN Inhibitor of growth protein 3 Q9NXR8 513 VLDELKNMKC P53 inducible protein Q9UN29 514 PQDYPDKKSLP DNA polymerase alpha catalytic P09884 subunit (EC 2.7.7.7) 515 NLLPKLHIV Chloride intracellular channel protein Q9Y696 4 (Intracellular chloride ion channel protein p64H1 516 LAAAGGPGQGWA Paired mesoderm homeobox protein Q99453 2B (Paired likehomeobox 2B) (PHOX2B homeodomain protein) (Neuroblastoma Phox) 517 GTPPPPGKPE PRB3 protein P81489 518 SQGAVGLAGV Protein patched homolog 1 (PTC1) Q13635 (PTC) 519 ELKKINYQV Protein patched homolog 1 (PTC1) Q13635 (PTC) 520 KLFQDLQDL Rap guanine nucleotide exchange Q9Y4G8 factor 2 (Neural RAP guanine nucleotide exchange protein)(nRap GEP)(PDZ domain-containing guanine nucleotide exchange factor 1)(PDZ-GEF1) 521 EAIVSHEKN Pecanex-like protein 1 (Pecanex Q96RV3 homolog) 522 GLLPQVNTFV Pecanex like protein 1 (Pecanex Q96RV3 homolog)- 523 KAYDVEREL GC-1-related estrogen receptor alpha Q8TDE4 coactivator short isoform 524 DVLESWLDF PHD finger Q86U89 525 TMLVLVIRG Hypothetical protein Q6N038 DKFZp686C07187 526 DVAQLQALLQ Phosphatidylinosito1-4,5- P42338 bisphosphate 3-kinase catalytic subunit beta isoform (EC 2.7.1.153) (PI3-kinase p110 subunit beta) (PtdIns-3-kinase p110) 527 QIIEANYHS Phosphodiesterase 8A, isoform 1 Q6P9H3 528 YVTDVLYRV Serine/threonine-protein kinase Q96Q15 SMG1 (EC 2.7.11.1)(SMG-1) (hSMG-1)(Lambda/iota protein kinase C-interacting protein) (Lambda-interacting protein)( 529 FLDDEVIEL PiggyBac transposable element Q8N328 derived 3 530 VICILPNDDK PIWIL3 protein Q7Z3Z3 531 IQNSQLQLQ Homeobox protein PKNOX1 P55347 (PBX/knotted homeobox 1) 532 FAYLLTYMA Transmembrane protein 115 (Protein Q12893 PL6) 533 GLIDSLVHYV Plakophilin-2 Q99959 534 REDHPARP Plectin 6 Q6S380 535 FLLDPVKGERL Plectin 1 (PLTN)(PCN) Q15149 (Hemidesmosomal protein 1)(HD1) 536 RGQNLDVVQ Plexin B1; plexin 5; semaphorin O43157 receptor 537 SLTGHISTV Pleiotropic regulator 1 O43660 538 EPLRVPPDL Blood vessel epicardial substance Q8NE79 (hBVES)(Popeye domain-containing protein 1)(Popeye protein 1) 539 EIPVLNELPV Carboxypeptidase-like protein X2 Q8N436 precursor 540 LYIPAMAFI YIF1B protein YIF1B protein 541 SLLQHLIGL Melanoma antigen preferentially P78395 expressed in tumors (Pr4eferentially expressed antigen of melanoma) (OPA-interacting protein 4) 542 ISSMLVLFF Splice isoform 2 of Q9H7F0 Q9H7F0-2 543 ENHSSQTDNI P2Y purinoceptor 13 (P2Y13)(G- Q9BPV8 protein coupled receptor 86)(G- protein coupled receptor 94) 544 ILMGVLKEV Putative pre-mRNA-splicing factor O43143 ATP-dependent RNA helicase DHX15 (EC 3.6.1.-)(DEAH box protein 15)(ATP-dependent RNA helicase #46) 545 VLFENTDSVHL HUMAN RNA-binding protein 34 P42696 (RNA-binding motif protein 34) 546 INMRIQDL Prolyl 4-hydroxylase alpha-1 subunit P13674 precursor (EC 1.14.11.2)(4-PH alpha-1)(Procollagen-proline,2- oxoglutarate-4-dioxygenase alpha-1 subunit) 547 KTDKTLVLL Profilin-1 P07737 548 GLIEILKKV Programmed cell death protein 5 O14737 (TFAR19 protein)(TF-1 cell apoptosis-related gene 19 protein) 549 NMVDIIHSV Propionyl-CoA carboxylase beta P05166 chain, mitochondrial precursor (EC 6.4.1.3) 550 ILDAGGHNVTI 26S proteasome non-ATPase Q99460 regulatory subunit 1 (26S proteasome regulatory subunit RPN2)(26S proteasome regulatory subunit S1) (26S proteasome subunit p112) 551 YMNLEKPDFI 26S proteasome non-ATPase Q99460 regulatory subunit 1 (26S proteasome regulatory subunit RPN2)(26S proteasome regulatory subunit S1) (26S proteasome subunit p112) 552 SLADIAQKL 26S proteasome non-ATPase O43242 regulatory subunit 3 (26S proteasome regulatory subunit S3)(Proteasome subunit p58) 553 QLVDIIEKV Proteasome activator complex P61289 subunit 3 (Proteasome activator 28- gamma subunit)(PA28gamma) (PA28g)(Activator of multicatalytic protease subunit 3)(11S regulator complex gamma subunit)(REG- gamma)(Ki nuclear autoantigen) 554 SLLKVDQEV Proteasome activator complex P61289 subunit 3 (Proteasome activator 28- gamma subunit)(PA28gamma) (PA28g)(Activator of multicatalytic protease subunit 3)(11S regulator complex gamma subunit)(REG- gamma)(Ki nuclear autoantigen) 555 QILRLLHIE Protein C14orf166 Q9Y224 556 EMGGGENNLK Protein KIAA1219 Q86X10 557 NLAEKLIGV Protein KIAA1219 Q86X10 558 EKSVSVQTNL Protein KIAA1688 Q9C0H5 559 GLLDSLTGILN Protein Plunc precursor (Palate lung Q9NP55 and nasal epithelium clone protein) (Lung-specific protein X) (Nasopharyngeal carcinoma-related protein)(Tracheal epithelium- enriched protein)(Secretory protein in upper respiratory tracts) 560 SLLPPDALVGL Protein transport protein Sec23B Q15437 561 LEEKNTLIQEL Liprin-alpha-2 (Protein tyrosine O75334 phosphatase receptor type f polypeptide-interacting protein alpha- 2)(PTPRF-interacting protein alpha- 2) 562 LLSESNERL Liprin-alpha-2 (Protein tyrosine O75334 phosphatase receptor type f polypeptide-interacting protein alpha- 2)(PTPRF-interacting protein alpha- 2) 563 LADLGSLESP Protocadherin gamma A12 precursor O60330 (PCDH-gamma-A12)(Cadherin-21) (Fibroblast cadherin 3) 564 QLLKFQLNK Protocadherin gamma A10 precursor Q9Y5H3 (PCDH-gamma-A10) 565 LLAEAVLTYL Leucine carboxyl methyltransferase 2 O60294 (EC 2.1.1.-)(p21WAF1/CIP1 promoter-interacting protein) 566 QLLREPHLQ KIAA1636 protein Q9HCD6 567 TIPNLEQIE Probable G-protein coupled receptor Q9UJ42 160 568 KLWEAESKL Protein C21orf45 Q9NYP9 569 IFHLHELPE Periodic tryptophan protein 2 Q15269 homolog 570 KLFNDAIRL Rab-like protein 2B Q9UNT1 571 FENQEVQAI Cell cycle checkpoint protein RAD17 O75943 (hRad17)(RF-C/activator 1 homolog) 572 EYVEKFYRI DNA repair protein RAD50 (EC 3.6.-.-) Q92878 (hRAD50) 573 QIDEIRDK DNA repair protein RAD50 (EC 3.6.-.-) Q92878 (hRAD50) 574 FLHEKLESL Ras GTPase-activating protein 1 P20936 (GTPase-activating protein)(GAP) (Ras p21 protein activator) (p120GAP)(RasGAP) 575 FELNNELKM Ras guanine nucleotide exchange Q9UK56 factor 2 576 LLSNNNQAL Ras-GTPase-activating protein- Q13283 binding protein 1 (EC 3.6.1.-)(ATP- dependent DNA helicase VIII)(GAP SH3-domain-binding protein 1) (G3BP-1)(HDH-VIII) 577 VLCGNKSDLE Ras-related protein Rab-27A (Rab- P51159 27)(GTP-binding protein Ram) 578 LLMYDIAN Ras-related protein Rab-3D O95716 579 SQVNILSKIVSR Nuclear pore complex protein P57740 Nup107 (Nucleoporin Nup107)(107 kDa nucleoporin) 580 VMFNGKVYL Receptor-interacting factor 1 Q86XS4 581 LEVEVIEAR Regulating synaptic membrane Q9UJD0 exocytosis protein 3 (Nim3)(Rab-3 interacting molecule 3)(RIM 3) (RIMS gamma) 582 TLLRGIEW Regulator of G protein signaling Q86UV0 protein (Regulator of G-protein signalling like 1) 583 PDFTELDLQ MHC class II regulatory factor RFX1 P22670 (RFX)(Enhancer factor C)(EF-C) 584 DVLFALFSKL Retinoblastoma-associated protein P06400 (PP110)(P105-RB) 585 RSGERKAVQA Roundabout homolog 3 precursor Q96MS0 (Roundabout-like protein 3) 586 GLNEEIARV Retinoblastoma-associated protein O14777 HEC (Kinetochore associated 2) 587 FLFQEPRSI Retinoblastoma-associated protein Q9UK61 RAP140 588 FLFQEPRSIVT Retinoblastoma-associated protein Q9UK61 RAP140 589 KEVDILNLP AT-rich interactive domain- P29374 containing protein 4A (ARID domain-containing protein 4A) (Retinoblastoma-binding protein 1) 590 YKLPMEDLK Jumonji/ARID domain-containing P29375 protein 1A (Retinoblastoma-binding protein 2)(RBBP-2) 591 TMVDRIEEV Jumonji/ARID domain-containing P29375 protein 1A (Retinoblastoma-binding protein 2)(RBBP-2) 592 VEGLLTLSDFDL RhoGTPase regulating protein Q6RJU5 variant ARHGAP20-1ad 593 WMLDKLTGV 40S ribosomal protein S4, Y isoform Q8TD47 2 594 LLKHLLLLL RNA binding motif Q13380 595 ALLSRLEQI RNA binding protein (Autoantigenic, Q2M365 hnRNP-associated with lethal yellow), long isoform- 596 DVYEDELVP RNA-binding protein Q8NI52 597 VMLGGRNIKV Ro ribonucleoprotein-binding protein Q9UHX1 1 (SIAHBP1 protein) 598 RLDELGGVYL HUMAN OTTHUMP00000030902 Q5JYR6 599 FEDKLIEDL Ryanodine receptor 2 (Cardiac Q92736 muscle-type ryanodine receptor) (RyR2)(RYR-2)(Cardiac muscle ryanodine receptor-calcium release channel)(hRYR-2) 600 QLIDKVWQL SEC14-like protein 1 Q92503 601 FLLEPQMKV Secreted and transmembrane protein Q8WVN6 1 precursor (Protein K12) 602 ILNEDGSPNL Neudesin precursor (Neuron-derived Q9UMX5 neurotrophic factor) 603 LLAILILAL P-selectin glycoprotein ligand 1 Q14242 precursor (PSGL-1)(Selectin P ligand)(CD162 antigen) 604 SMNRGGYMP Semaphorin-6D precursor Q8NFY4 605 EFIDGSLQM Serine/threonine/tyrosine-interacting Q8WUJ0 protein (Protein tyrosine phosphatase-like protein) 606 ILVVYVIGL Olfactory receptor 8G5 (Olfactory Q8NG78 receptor OR11-298) 607 TLSERLWLG Shb-like adapter protein, Shf Q7M4L6 608 VLWDRTFSL Signal transducer and activator of P42224 transcription 1-alpha/beta (Transcription factor ISGF-3 components p91/p84) STAT1 609 NVNFFTKPP Signal transducer and activator of P40763 transcription 3 (Acute-phase response factor) 610 ETFSGVYKK 40S ribosomal protein S7 P62081 611 QLDDLKVEL 60S ribosomal protein L35 P42766 612 MEDLIHEI 60S ribosomal protein L7 P18124 613 QTDVDNDLV Thrombospondin-2 precursor P35442 614 LLIDPPRYI C3 and PZP-like alpha-2- Q8IZJ3 macroglobulin domain containing 8 615 PSIPTSAQHV C3 and PZP-like alpha-2- Q8IZJ3 macroglobulin domain containing 8 616 FLDEPTNHL ATP-binding cassette sub-family F Q9UG63 member 2 (Iron-inhibited ABC transporter 2) 617 KMDDPDYWRTV Ribosome biogenesis protein BOP1 Q14137 (Block of proliferation 1 protein) 618 LANVQQVQI CDNA FLJ13765 fis, clone Q9H8C5 PLACE4000128, weakly similar to Mus musculus putative transcription factor mRNA 619 SLFVVILVT CD200 cell surface glycoprotein Q6Q8B3 receptor isoform 2 variant 2 620 ARTIKIRNI LRRC58 protein Q96CX6 621 LVLTSGIVFV Claudin-6 (Skullin 2) P56747 622 VISFDKLKL T-box transcription factor TBX18 (T- O95935 box protein 18) 623 DLMELYKV INTS7 protein Q8WUH5 624 LQRRKPTGAF FRAS1-related extracellular matrix Q5SZK8 protein 2 precursor (ECM3 homolog) 625 KVNNEKFRT Zinc finger protein 318 (Endocrine Q5VUA4 regulatory protein) 626 SLDQPTQTV Eukaryotic translation initiation Q99613 factor 3 subunit 8 (eIF3 p110) (eIF3c) 627 SVTSEGIKAV HUMAN LOC196394 protein Q8IY45 628 ISLSEPAKPG Hypothetical protein FLJ44216 Q8NDZ2 629 ILDKKVEKV Heat shock protein HSP 90-beta P08238 (HSP 84)(HSP 90) 630 KLSAEVESLK Sarcoma antigen NY-SAR-41 (NY- Q5T9S5 SAR-41) 631 VTWDAALYI Protein FAM86A Q96G04 632 YLLPKDIKL Ras-like family 11 member A Q6T310 (OTTHUMP00000018162) 633 RLLEDGEDFNL Keratin, type I cytoskeletal 18 P05783 (Cytokeratin-18)(CK-18) 634 RVLPYPFTH U3 small nucleolar RNA-associated Q9BVJ6 protein 14 homolog A (Antigen NY- CO-16) 635 QNQERLER Hypothetical protein Q68DM0 DKFZp781D1722 636 QDNIKELEL Chromosome-associated kinesin O95239 KIF4A (Chromokinesin) 637 ILKQRDNEI Kinesin-like protein KIF6 Q6ZMV9 638 QNELDNVSTL Myosin-10 (Myosin heavy chain, P35580 nonmuscle IIb)(Nonmuscle myosin heavy chain IIb) 639 NIDLLDDGSN Hypothetical protein C17orf57 Q8IY85 640 VLQSNIQHV Similar to peptide N-glycanase Q9BVR8 homolog (S. cerevisiae) 641 VFFDIAVDGEPL Peptidyl-prolyl cis-trans isomerase A P62937 (EC 5.2.1.8) 642 DFHFPKFSI Serpin A13 precursor Q6UXR4 643 SYVNLPTIAL 40S ribosomal protein SA (p40) P08865 (34/67 kDa laminin receptor)(Colon carcinoma laminin-binding protein) (NEM/1CHD4)(Multidrug resistance-associated protein MGr1- Ag) 644 SNLEHLGHE N-acetylglucosamine-1- Q9UJJ9 phosphotransferase subunit gamma precursor 645 LKLKLTAVEK Liprin-beta-1 (Protein tyrosine Q86W92 phosphatase receptor type f polypeptide-interacting protein- binding protein 1) 646 GLKGRVFEV 40S ribosomal protein S3a P61247 647 SLADLQNDEV 40S ribosomal protein S3a P61247 648 NNLPHLQVV LOC124512 protein (Fragment) Q86XA0 649 ISFGGSVQL Hypothetical protein MGC26744 Q96KX1 650 SILDQILQ Hypothetical protein LOC122258 Q96KW9 651 TLSDLRVYL Sulfiredoxin-1 (EC 1.8.98.2) Q9BYN0 652 EAFVNSKN Basalin Q5QJ38 653 VTWDAALYL Protein FAM86A Q96G04 654 VLDDKLVFV Transmembrane protein 16F Q4KMQ2 655 YLLDLHSYL TEB4 protein O14670 656 FLALAVIQL SLC10A5 Q5PT55 657 TLAEVSTRL Serine/threonine-protein kinase P57059 658 VIEVYQEQI SNF1-like kinase 1 (EC 2.7.11.1) Q6P094 LOC391257 protein 659 RLWEEAVKA Zinc finger protein 161 (Putative Q14119 transcription factor DB1) 660 SLKTLMLR Slit homolog 2 protein precursor O94813 (Slit-2) 661 EIKKKFKL FYN-binding protein (FYN-T- O15117 binding protein) 662 VHKEMFIMV Jumonji/ARID domain-containing P41229 protein 1C (SmcX protein)(Xe169 protein) 663 VHKEMFIMV Jumonji/ARID domain-containing Q9BY66 protein 1D (SmcY protein) (Histocompatibility Y antigen) 664 LAGSEVALAGV Monocarboxylate transporter 3 (MCT O95907 3) 665 IPHDLFTEL Solute carrier family 4 sodium Q6U841 bicarbonate cotransporter-like member 10- 666 FLADPDTVNHLL Sorting nexin 14, isoform a Q6NUI7 667 RVADRLYGV Sorting nexin-4 O95219 668 HRPDLLDY Spectrin beta chain, brain 4 (Spectrin, Q9NRC6 non-erythroid beta chain 4) 669 TLDENHPSI Spermatogenesis-associated protein 7 Q9P0W8 (Spermatogenesis-associated protein HSD3) 670 TLAEIAKVEL Non-POU domain-containing Q15233 octamer-binding protein (NonO) protein)(54 kDa nuclear RNA-and DNA-binding protein)(p54(nrb)) (p54nrb)(55 kDa nuclear protein) 671 DVAVEAIRL Cohesin subunit SA-1 (Stromal Q8WVM7 antigen 1)(SCC3 homolog 1) 672 LMVDHVTEV Steroid receptor RNA activator Q9HD15 isoform 1 673 SLYEMVSRV Structure-specific recognition protein Q08945 1 (SSRP1)(Recombination signal sequence recognition protein)(T160) (Chromatin-specific transcription elongation factor 80 kDa subunit) 674 SINPKRAKL Suppressor of hairy wing homolog 2 Q86YH2 (5′OY11.1)(Zinc finger protein 632) 675 NMYGKVVTV Transcription elongation factor SPT5 O00267 (hSPT5)(DRB sensitivity-inducing factor large subunit)(DSIF large subunit)(DSIF p160)(Tat- cotransactivator 1 protein)(Tat-CT1 protein)- 676 SLFATEQL Synaptogyrin-3 O43761 677 RLQEGDKILSV Synaptojanin-2-binding protein P57105 (Mitochondrial outer membrane protein 25) 678 AMFDKKVQL Synemin Q8TE61 679 ALNELLQHV Talin-1 Q9Y490 680 RVVSMAALAM TAR RNA loop binding protein v (TAR(HIV)RNA binding protein 1) 681 GIIMQIIDV Taste receptor type 2 member 3 Q9NYW6 (T2R3) 682 IFNAIALFL Taste receptor type 2 member 40 P59535 (T2R40)(T2R58)(G-protein coupled receptor 60) 683 LEQGLFSKV Oxidoreductase HTATIP2 (EC Q9BUP3 1.1.1.-)(HIV-1 TAT-interactive protein 2) 684 KFMHMGKRQK Transcription initiation factor TFIID P49848 subunit 6 (Transcription initiation factor TFIID 70 kDa subunit) (TAF(II)70)(TAFII-70)(TAFII-80) (TAFII80) 685 SNFGNEKL TRA@ protein Q6PIP7 686 FLLDKKIGV T-complex protein 1 subunit beta P78371 (TCP-1-beta)(CCT-beta) 687 RSLAASNPIL Telomerase-binding protein EST1A Q86US8 (Ever shorter telomeres 1A) (Telomerase subunit EST1A)(EST1- like protein A)(hSmg5/7a) 688 EMESLTGHQ Tumor endothelial marker 6 Q96PE0 (Hypothetical protein TEM6) 689 LDFQEELEV Ras GTPase-activating-like protein Q13576 IQGAP2 690 SPNSEGDAGDL Tetratricopeptide repeat protein 15 Q8WVT3 (TPR repeat protein 15) 691 LVYLNESSVLH Myosin-18A (Myosin XVIIIa) Q92614 (Myosin containing PDZ domain) (Molecule associated with JAK3 N- terminus)(MAJN) 692 VAGIKVNQVK Polycystic kidney and hepatic disease Q8TCZ9 1 precursor (Fibrocystin) 693 ILYELQVEL TMC4 protein Q7Z5M3 694 EVLDELYRV MDC-3.13 isoform 1 (TNFAIP8 Q9UER5 protein) 695 TNIEDGVFET Toll-like receptor 8 precursor Toll-like receptor 8 precursor 696 EIRKNEGQI Tolloid-like protein 1 precursor (EC O43897 3.4.24.-) 697 IAAKILSYN DNA topoisomerase I, mitochondrial Q969P6 precursor (EC 5.99.1.2)(TOP1mt) 698 LYGRHFNYL PAP associated domain-containing Q8NDF8 protein 5 (EC 2.7.7.-) (Topoisomerase-related function protein 4-2)(TRF4-2) 699 NLFNKYPAL Plastin-3 (T-plastin) P13797 700 YLDEIVKEV Translocated promoter region (To Q5SWY0 activated MET oncogene) 701 ENHSSQTDNI P2Y purinoceptor 13 (P2Y13)(G- Q9BPV8 protein coupled receptor 86)(G- protein coupled receptor 94) 702 RTHMLSSL Transcript Y 5 Q9BXH6 703 QATIAPVTV Transcription factor Sp4 (SPR-1) Q02446 704 NLFRAPIYL Transcription initiation factor TFIID P21675 subunit 1 (EC 2.7.11.1) (Transcription initiation factor TFIID 250 kDa subunit)(TAF(II)250) (TAFII-250)(TAFII250)(TBP- associated factor 250 kDa)(p250) (Cell cycle gene 1 protein) 705 KLEEEQEKNQL Transcriptional repressor CTCFL Q8NI51 (CCCTC-binding factor)(Brother of the regulator of imprinted sites)(Zinc finger protein CTCF-T)(CTCF paralog 706 LNVDTPFPL Transducer of regulated CREB Q6UUV7 protein 3 707 ILYELKVEL Transmembrane channel-like protein Q7Z404 4 708 KFMHMGKRQK Transcription initiation factor TFIID P49848 subunit 6 (Transcription initiation factor TFIID 70 kDa subunit) (TAF(II)70)(TAFII-70)(TAFII-80) (TAFII80) 709 HSDEGGVASL Trophinin-associated protein (Tastin) Q12815 (Trophinin-assisting protein) 710 AMLTGELKKA Tryptophanyl-tRNA synthetase (EC P23381 6.1.1.2)(Tryptophan--tRNA ligase) (TrpRS)(IFP53)(hWRS) 711 VFPTHVFPT Tubulin, gamma complex associated Q5T9Y2 protein 3 712 KELAELRESTS Tumor necrosis factor ligand P48023 superfamily member 6 (Fas antigen ligand)(Fas ligand)(CD178 antigen) (CD95L protein)(Apoptosis antigen ligand)(APTL)[Contains: Tumor necrosis factor ligand superfamily member 6, membrane form 713 LTDKEGWIL Tumor necrosis factor, alpha-induced Q13829 protein 1, endothelial (B12 protein) 714 VVTYKNENI Netrin receptor DCC precursor P43146 (Tumor suppressor protein DCC) (Colorectal cancer suppressor) 715 TVAEGLIED Adipocyte-derived leucine Q9NZ08 aminopeptidase precursor (EC 3.4.11.-)(A-LAP)(ARTS-1) (Aminopeptidase PILS)(Puromycin- leucyl-specific aminopeptidase)(PILS-AP)(Type 1 tumor necrosis factor receptor shedding aminopeptidase 716 NEKIKKDEL U1 small nuclear ribonucleoprotein A P09012 (U1 snRNP protein A)(U1A protein) (U1-A 717 ILDESHERV U6 snRNA-associated Sm-like O95777 protein LSm8 718 NLYSDYILN Ubiquitin-protein ligase E3A (EC Q05086 6.3.2.-)(E6AP ubiquitin-protein ligase)(Oncogenic protein-associated protein E6-AP)(Human papillomavirus E6-associated protein) 719 RYVNGHAK Ubiquitin carboxyl-terminal Q9Y6I4 hydrolase 3 (EC 3.1.2.15)(Ubiquitin thioesterase 3)(Ubiquitin-specific- processing protease 3) (Deubiquitinating enzyme 3) 720 KLLDLELAPS UBX domain-containing protein 2 Q92575 721 YLYDLNHTL UNC93 homolog B1 (UNC-93B Q9H1C4 protein)(hUNC93B1) 722 FFFWLMEL Splice isoform 5 of Q9H171 Q9H171-5 723 ELSSLKETHI CDNA FLJ46282 fis, clone Q6ZRK6 TESTI4031066 724 KLGSVPVTV CCDC73 protein Q6P5Q7 725 ALWERIEGV Caspase recruitment domain- Q9BWT7 containing protein 10 (CARD- containing MAGUK protein 3) (Carma 3) 726 VKAQEILR Caspase recruitment domain- Q9BWT7 protein 10 (CARD- containing MAGUK protein 3) (Carma 3) 727 ANVDAIVVSV Chromatin-specific transcription Q9Y5B9 elongation factor FACT 140 kDa subunit 728 CKDGEDSIIR Beta-defensin 120 precursor Q8N689 729 DNTKKSDKT Alpha-catulin (Catenin alpha-like Q9UBT7 protein 1)(Alpha-catenin-related protein) 730 EFLGDSIMQ Ribonuclease III (EC 3.1.26.3) Q9NRR4 (RNase III) 731 EFLQEGLEK Seizure related 6 homolog Q53EL9 732 FLLKCLEQV Granulocyte colony-stimulating P09919 factor precursor (G-CSF) (Pluripoietin)(Filgrastim) (Lenograstim) 733 FLTDSNNIKEV Lysyl-tRNA synthetase Q9HB23 734 GGVQELLNQQ Protein C6orf130 Q9Y530 735 GKPRRKSNL Melanophilin (Exophilin-3) Q9BV36 (Synaptotagmin-like protein 2a)(Slp homolog lacking C2 domains a) 736 HIKEELMHG Novel protein (Possible ortholog of Q5VTR6 mouse phosphoinositide-3-kinase adaptor protein 1 (Pik3ap1) 737 HIPFFLHN AER61 glycosyltransferase Q6P985 738 ILEKKVEKV Heat shock protein HSP 90-alpha P07900 (HSP 86) 739 ILMEHIHKL 60S ribosomal protein L19 P84098 740 KASQLGIFISKV PDZ domain-containing protein 11 Q5EBL8 741 KILEVMHTK Dedicator of cytokinesis 11-; Q5JSL3 Cdc42-associated guanine nucleotide exchange factor ACG/DOCK11 742 LAVGTSPVLA Hypothetical protein FLJ26930 Q6ZNX6 743 LLAEEARKL Laminin gamma-1 chain precursor P11047 (Laminin B2 chain) 744 LLGICFCIA ATP-binding cassette transporter sub- Q96J66 family C member 11 (Multidrug resistance-associated protein 8) 745 LMAEMGVHSV Uridine/cytidine kinase-like 1 Q9NWZ5 746 ISRLENITV Butyrophilin-like protein 8 precursor Q6UX41 747 MISLPGPLVTN Endothelial cell-selective adhesion Q96AP7 molecule precursor 748 MLLDVMHTV Poly(A)-specific ribonuclease PARN O95453 (EC 3.1.13.4)(Polyadenylate- specific ribonuclease)(Deadenylating nuclease)(Deadenylation nuclease) 749 NVMNLIDFV Voltage-gated potassium channel Q96RP8 KCNA7 750 NVTMKDNKI F-box protein 11 Q52ZP1 751 PRSNIDVNI rythrocyte membrane protein band Q7Z5S1 4.1 like 5 752 PSAQPLLSL CDNA FLJ45015 fis, clone Q6ZT30 BRAWH3014639 753 QLKESKLKI FAM13A1_v2 protein Q24JP0 754 RDAPHLPDG Hypothetical protein FLJ26432 Q6ZP70 755 RLPPEGILHNV VPS13D-1A protein Q709C5 756 SEGAEYDDQT Coagulation factor VIII precursor P00451 (Procoagulant component) (Antihemophilic factor)(AHF) 757 SLFERLVKV NFX1-type zinc finger-containing Q9P2E3 protein 1 758 SLLDKIIGA Polymerase I and transcript release Q6NZI2 factor (PTRF protein) 759 SMMDVDHQI T-complex protein 1 subunit epsilon P48643 (TCP-1-epsilon)(CCT-epsilon) 760 TLDEKIEKV Probable ATP-dependent RNA Q96GQ7 helicase DDX27 (EC 3.6.1.-)(DEAD box protein 27) 761 TLLEDGTFKV HSCARG Q9HBL8 762 TVLKTKFSS CDNA FLJ43956 fis, clone Q6ZU72 TESTI4015681 763 VIFEDVGRQVL Mitochondrial-processing peptidase Q10713 alpha subunit, mitochondrial precursor (EC 3.4.24.64)(Alpha- MPP) 764 YILDINPLL CDNA FLJ45287 fis, clone Q6ZSR0 BRHIP3002124 765 YKTFSTSMMLL Hypothetical protein C12orf62 Q96I36 766 RLPPEGILHNV VPS13D-2A protein Q709C4 767 LLGPRVLSP CDNA FLJ32009 fis, clone Q96DN2 NT2RP7009498, weakly similar to FIBULIN-1, ISOFORM A 768 FIILLVTYI Transient receptor potential cation Q9HBA0 channel subfamily V member 4 (TrpV4)(osm-9-like TRP channel 4) (OTRPC4)(Vanilloid receptor-like channel 2)(Vanilloid receptor-like protein 2)(VRL-2) 769 FYDIETLK Vascular endothelial growth factor D O43915 precursor (VEGF-D)(c-fos-induced growth factor)(FIGF) 770 WMAPESIFDKI Vascular endothelial growth factor P17948 receptor 1 precursor (EC 2.7.10.1) (VEGFR-1)(Vascular permeability factor receptor)(Tyrosine-protein kinase receptor FLT)(Flt-1) (Tyrosine-protein kinase FRT)(Fms- like tyrosine kinase 1) 771 LLDQQNPDE Proto-oncogene C-crk (P38)(Adapter P46108 molecule crk) 772 VMFKKIKSFEV VDUP1 protein (Thioredoxin Q9H3M7 interacting protein) 773 KLLEGEESRISL Vimentin P08670 774 KLLEGEESRISL HUMAN CTCL tumor antigen HD- Q548L2 CL-06 (Vimentin variant) 775 RILGAVAKV Vinculin (Metavinculin) P18206 776 SLSMVNHRL Integrin alpha-3 precursor P26006 (Galactoprotein B3)(GAPB3)(VLA- alpha chain)(FRP-2)(CD49c antigen)[Contains: Integrin alpha-3 heavy chain; Integrin alpha-3 light chain] 777 VGQADGGLSVLR Voltage-dependent T-type calcium O95180 channel alpha-1H subunit (Voltage- gated calcium channel alpha subunit Cav3.2)(Low-voltage-activated calcium channel alpha1 3.2 subunit) 778 DVATILSRR Wiskott-Aldrich syndrome protein Q8IV90 family member 4 (WASP-family protein member 4) 779 PKFEVIEKPQA ATP synthase coupling factor 6, P18859 mitochondrial precursor (EC 3.6.3.14)(ATPase subunit F6) 780 NCTTIDDSLAI Proto-oncogene protein Wnt-3 P56703 precursor 781 ILPTVILAN myloid beta A4 precursor protein- Q99767 binding family A member 2 (Neuron- specific X11L protein)(Neuronal Munc18-1-interacting protein 2) (Mint-2)(Adapter protein X11beta) 782 EFLELSAAQE Zinc finger CCHC domain- Q8N8U3 containing protein 5 783 SLTDKVQEA Myeloid/lymphoid or mixed-lineage Q59FF2 leukemia (Trithorax homolog, Drosophila) variant 784 SKNSALEYQL Zinc finger protein DZIP1 (DAZ- Q86YF9 interacting protein 1/2) 785 LQDVEEVEI Hypothetical protein Q69YS5 DKFZp761O1618 786 FLDEPTNHL ATP-binding cassette sub-family F Q9UG63 member 2 (Iron-inhibited ABC transporter 2) 787 KMDDPDYWRTV Ribosome biogenesis protein BOP1 Q14137 (Block of proliferation 1 protein) 788 LANVQQVQI CDNA FLJ13765 fis, clone Q9H8C5 PLACE4000128 789 KLDPTKTTL NDRG1 protein (N-myc downstream Q92597 regulated gene 1 protein) 790 HLTYLNVYL Pre-mRNA splicing factor ATP- Q92620 dependent RNA helicase PRP16 791 ALWDKLFNL Nesprin 2 (Nuclear envelope spectrin Q9NU50 repeat protein 2) 1514 KIMDQVQQA Adenomatous polyposis coli P25054 1515 RLQEDPPAGV Ubiquitin conjugating enzyme E2 P49459 1516 KLDVGNAEV B cell receptor-associated protein P5572 BAP31 (CDM protein) 6c6-AG 1517 FLYDDNQRV Topoisomerase II-alpha P11388 1518 FLYDDNQRV Topoisomerase II beta Q02880 1519 ALMEQQHYV Integrin beta8 subunit precursor P26012 1520 YLMDTSGKV Replication Protein A P27694 1521 ILDDIGHGV Abl Binding protein 3 U31089 1522 LLDRFLATV Cyclin I Q14094 1523 LLIDDKGTIKL Cell Division Control Protein 2 P06493 (CDC2) 1524 RLYPWGVVEV Septin 2 (NEDD5) Q15019 1525 KLQELNYNL STAT1 alpha/beta P42224 1526 ILIEHLYGL LDL Receptor-related protein (LRP) Q07954 1527 YLIELIDRV TACE (ADAM17) NP-068604 1528 NLMEQPIKV Junction plakoglobin (gamma P14923 catenin) 1529 FLAEDALNTV EDDR1 Q08345 1530 TLLNVIKSV IP3 receptor type II Q14571 1531 MLKDIIKEY Melanoma-associated antigen D2 Q9UNF1 (MAGE-D2 antigen)(MAGE-D) (Breast cancer-associated gene 1 protein)(BCG-1)(11B6) (Hepatocellular carcinoma-associated protein JCL-1) 1532 TSYVKVLEH Melanoma-associated antigen 4 P43358 (MAGE-4 antigen)(MAGE-X2) (MAGE-41) 1533 HEYLKAFKV HUMAN Retinoblastoma-like Q08999 protein 2 (130 kDa retinoblastoma- associated protein)(PRB2)(P130) (RBR-2) -
TABLE 3 SEQ ID NO, Parent Protein Identification and SwissProt Identification Number for full-length sequences 792-1513 Parent SwissProt SEQ Identification ID NO: Parent Sequence Identification No. 792 BCL-6 corepressor long isoform_ Q6W2J9 793 E1B_19K/Bcl-2-interacting protein Nip3 Q12983 794 Similar to Heat shock protein HSP 90-beta P08238 (HSP 84) (HSP 90) 795 Cytochrome P450 11B2, mitochondrial P19099 precursor 796 2′-5′oligoadenylate synthetase 3 Q2HJ14 797 26S protease regulatory subunit 4 (P26s4) P62191 798 26S proteasome non-ATPase regulatory P51665 subunit 7 799 26S proteasome non-ATPase regulatory O00487 subunit 14 800 40S ribosomal protein S16 P62249 801 40S ribosomal protein S6 P62753 (Phosphoprotein NP33) 802 40S ribosomal protein S9 P46781 803 60S ribosomal protein L10a (CSA-19) P62906 804 6-phosphofructo-2-kinase/fructose-2,6- biphosphatase 4 (6PF-2-K/Fru-2,6-P2ASE Q16877 testis-type isozyme) 805 Cleavage and polyadenylation specificity Q9UKF6 factor, 73 kDa subunit (CPSF 73 kDa subunit) 806 A kinase anchor protein 10, mitochondrial O43572 precursor 807 Actin, cytoplasmic 1 (Beta-actin) P60709 808 Activated T-cell marker CD109 Q6YHK3 809 Activin receptor type 2A precursor P27037 (EC 2.7.11.30) 810 ADAM19 protein Q8TBU7 811 AP-1 complex subunit beta-1 Q10567 (Adapter-related protein complex 1 beta-1 subunit) (Beta-adaptin 1) 812 Adaptor-related protein NF01019537 Q9BYI8 813 Lung alpha/beta hydrolase protein 1 Q96SE0 814 Alpha-actinin-3 Q08043 815 Ankyrin-2 (Brain ankyrin) (Ankyrin-B) Q01484 816 Ankyrin repeat and SOCS box protein 17 Q8WXJ9 817 Anti-colorectal carcinoma heavy chain Q65ZQ1 818 APOBEC1 complementation factor Q9NQ94 (APOBEC1-stimulating protein) 819 Probable DNA dC->dU-editing enzyme Q96AK3 APOBEC-3D (EC 3.5.4.—) 820 Apolipoprotein-L4 precursor Q9BPW4 (Apolipoprotein L-IV) 821 Apoptosis stimulating of p53 protein 1 Q96KQ4 822 Nucleoporin 188 kDa (arachin) Q5SRE5 823 Protein ariadne-1 homolog (ARI-1) Q9Y4X5 (Ubiquitin-conjugating enzyme E2- binding protein 1) 824 Set1/Ash2 histone methyltransferase Q9UBL3 complex subunit ASH2 (ASH2-like protein) 825 ATP synthase F0 subunit 8 Q85KZ3 826 Splice isoform 2 of Q9H7F0 ATPase_ Q9H7F0 family_homolog_up-regulated_in_ senescence_cells_ 827 Probable phospholipid-transporting Q9Y2Q0 ATPase IA (EC 3.6.3.1) (Chromaffin granule ATPase II) 828 ATP-binding cassette A10 Q8WWZ4 829 ATP-binding cassette sub-family A Q9BZC7 member 2 (ATP-binding cassette transporter 2) (ATP-binding cassette 2) 830 Autoantigen RCD8 Q6P2E9 831 xonemal dynein heavy chain 8 Q96JB1 832 Butyrophilin-like protein 8 precursor Q6UX41 833 Ubiquitin carboxyl-terminal hydrolase 20 Q9Y2K6 (EC 3.1.2.15) 834 Bardet-Biedl syndrome 7 protein Q8IWZ6 (BBS2-like protein 1) 835 Large proline-rich protein BAT2 P48634 (HLA-B-associated transcript 2) 836 Bcl-2 related ovarian killer Q9UL32 837 Lipopolysaccharide-responsive and beige- P50851 like anchor protein (CDC4-like protein) 838 Splice isoform 3 of P35612 P35612-3 839 UDP-GlcNAc:betaGal beta-1,3-N- Q9Y2A9 acetylglucosaminyltransferase 3 (EC 2.4.1.—) 840 Cell growth inhibiting protein 39 Q2TTR2 841 BH3-interacting domain death agonist (BID) P55957 842 CD48 antigen precursor (B-lymphocyte P09326 activation marker BLAST-1) 843 Bone morphogenetic protein receptor type-2 Q13873 precursor (EC 2.7.11.30) 844 Bullous pemphigoid antigen 1, isoform 7 Q8WXK8 845 BRCA1 associated RING domain 1 variant Q53F80 846 Breast cancer type 2 susceptibility protein P51587 (Fanconi anemia group D1 protein) 847 Protein BRE (Brain and reproductive Q9NXR7 organ-expressed protein) (BRCA1/ BRCA2-containing complex subunit 45) 848 Breast cancer 1 early onset Q3LRJ0 849 Breast and ovarian cancer susceptibility Q7KYU6 protein 850 BTG2 protein (NGF-inducible anti- P78543 proliferative protein PC3) 851 Nuclear protein 5qNCA Q7LBC6 852 CAD protein [Includes: Glutamine-dependent P27708 carbamoyl-phosphate synthase (EC 6.3.5.5); Aspartate carbamoyltransferase (EC 2.1.3.2); Dihydroorotase (EC 3.5.2.3)] 853 Cadherin EGF LAG seven-pass G-type Q9NYQ7 receptor 3 precursor (Flamingo homolog 1) (hFmi1) (Multiple epidermal growth factor- like domains 2) (Epidermal growth factor-like 1) 854 Cadherin FIB3 Q6UW70 855 Integrin alpha-3 precursor (Galactoprotein B3) P26006 856 Calcineurin B homologous protein 2 O43745 (Hepatocellular carcinoma-associated antigen 520) 857 Calcium/calmodulin-dependent protein Q7Z7J9 kinase II inhibitor alpha (CaMKIINalpha) 858 Calpain-11 (EC 3.4.22.—) Q9UMQ6 859 Alpha-1 catenin (Cadherin-associated protein) P35221 (Alpha E-catenin) 860 Neural cell adhesion molecule variant Q59FY0 861 Ribosomal L1 domain-containing protein 1 O76021 (Cellular senescence-inhibited gene protein) 862 CENP-F kinetochore protein P49454 (Centromere protein F) (Mitosin) 863 Centaurin-delta 1 (Cnt-d1) (Arf-GAP, Q8WZ64 Rho-GAP, ankyrin repeat and pleckstrin homology domain-containing protein 2) 864 Centrosomal protein 2 (Centrosomal Nek2- Q9BV73 associated protein 1) (C-NAP1) 865 Pericentriol material 1 Q15154 866 Cervical cancer suppressor gene 5 Q8NFX8 867 T-complex protein 1 subunit zeta-2 Q92526 868 Chemokine-like factor (C32) Q9UBR5 869 Vacuolar protein sorting 13A Q96RL7 870 Chromodomain-helicase-DNA-binding O14647 protein 2 (EC 3.6.1.—) 871 FERM domain-containing protein 6 Q96NE9 872 Putative protein C21orf56 Q9H0A9 873 Adiponutrin (iPLA2-epsilon) Q9NST1 884 Coatomer subunit gamma-2 Q9UBF2 875 Sodium/potassium/calcium exchanger 2 Q9UI40 precursor 876 Exportin-1 (Chromosome region O14980 maintenance 1 protein homolog) 877 CUB and sushi domain-containing Q7Z407 protein 3 precursor 878 Cullin-7 (CUL-7) Q14999 879 Cyclic AMP-dependent transcription P18848 factor ATF-4 880 S-phase kinase-associated protein 1A P63208 (Cyclin A/CDK2-associated protein p19) 881 Cyclin-A1 P78396 882 Cyclin M3, isoform 1 Q8NE01 883 Cystathionine beta-synthase human homolog Q58H57 of Cynomolgus monkey gene product 884 Cytochrome P450 2E1 (EC 1.14.14.1) P05181 885 Keratin, type II cytoskeletal 8 P05787 886 CPEB2 protein Q3B8N6 887 Probable ATP-dependent RNA helicase P17844 DDX5 (EC 3.6.1.—) 888 Dedicator of cytokinesis protein 1 Q14185 889 Development and differentiation- O43150 enhancing factor 2 890 Probable ubiquitin carboxyl-terminal O00507 hydrolase FAF-Y (EC 3.1.2.15) 891 G2 and S phase expressed protein 1 Q9NYZ3 892 HUMAN CDNA FLJ30829 fis, clone Q96NI3 FEBRA2001790, highly similar to Xenopus laevis RRM-containing protein SEB-4 mRNA Q96B95 893 KIAA1799 protein 894 Peroxisomal proliferator-activated receptor Q9BYK8 A-interacting complex 285 kDa protein (EC 3.6.1.—) (ATP-dependent helicase PRIC285) 895 HUMAN KIAA1922 Q96PW6 896 Transcription elongation factor SPT5 O00267 (DLC-1) (deleted in liver cancer-1) 897 DNA damage-binding protein 1 Q16531 (Damage-specific DNA-binding protein 1) 898 DNA excision repair protein ERCC-6 Q03468 899 DNA polymerase alpha subunit B Q14181 (DNA polymerase alpha 70 kDa subunit) 900 DNA replication licensing factor MCM2 P49736 (Minichromosome maintenance protein 2 homolog) 901 DNA2-like homolog (EC 3.6.1.—) P51530 (DNA replication ATP-dependent helicase-like homolog) 902 Estrogen response element binding protein O77798 (cotton-top Tarmarin), DNA2-like homolog (human) 903 DNA damage-inducible transcript 3 P35638 (DDIT-3) (Growth arrest and DNA- damage-inducible protein GADD153) 904 DNA-directed RNA polymerase I largest 095602 subunit (EC 2.7.7.6) 905 DnaJ homolog subfamily C member 1 Q96KC8 906 Splice isoform 2 of P35462 P35462-2 907 RuvB-like 2 (EC 3.6.1.—) (48-kDa Q9Y230 TATA box-binding protein- interacting protein) 908 DRE1_protein Q9NXT9 909 Dynactin-1 (150 kDa dynein-associated Q14203 polypeptide) 910 Dynein heavy chain, cytosolic (DYHC) Q14204 911 Echinoderm microtubule associated Q6UYC9 protein-like 5 912 ECT2 protein (Epithelial cell- Q9H8V3 transforming sequence 2 oncogene) 913 Endothelial differentiation-related O60869 factor 1 (EDF-1) 914 Developmentally-regulated endothelial O43854 cell locus 1 protein) 915 Elongation factor 2 (EF-2) P13639 916 J domain protein C21orf55 Q9NX36 917 EMILIN-3 precursor (EMILIN-5) Q9NT22 (Elastin microfibril interface-located protein 5) 918 Synaptotagmin-like protein 4 (Exophilin-2) Q96C24 919 Enhancer of filamentation 1 (HEF1) Q14511 920 Band 4.1-like protein 3 (4.1B) (Differentially Q9Y2J2 expressed in adenocarcinoma of the lung protein 1) (DAL-1) 921 Epidermal growth factor receptor P42566 substrate 15 922 Epithelial membrane protein 3 (EMP-3) P54852 (YMP protein) 923 Zyxin (Zyxin-2) Q15942 924 Eukaryotic translation initiation factor 4 Q04637 gamma 1 925 F-actin capping protein beta subunit P47756 926 Protocadherin Fat 2 precursor (hFat2) Q9NYQ8 (Multiple epidermal growth factor-like domains 1) 927 KIAA1752 protein Q9C0B1 928 Fc alpha/mu receptor Q8WWV6 929 Low affinity immunoglobulin gamma P08637 Fc region receptor III-A precursor (IgG Fc receptor III-2) 930 FYVE, RhoGEF and PH domain- Q7Z6J4 containing protein 2 (Zinc finger FYVE domain-containing protein 4) 931 Fibroblast growth factor receptor-like 1 Q8N441 precursor (FGF receptor-like protein 1) 932 Fibroblast growth factor receptor 4 P22455 precursor (EC 2.7.10.1) 933 Fibroblast growth factor receptor 2 P21802 precursor (EC 2.7.10.1) (FGFR-2) 934 FK506-binding protein 7 precursor Q9Y680 (EC 5.2.1.8) 935 Glomulin (FKBP-associated protein) Q92990 (FK506-binding protein-associated protein) 936 FKSG73 Q9BWW1 937 Flavin containing monooxygenase Q53FW5 3 isoform 2 variant 938 Protein flightless-1 homolog Q13045 939 Guanylate-binding protein 4 Q96PP9 940 Filamin-A (Alpha-filamin) (Filamin-1) P21333 (Endothelial actin-binding protein) 941 FLJ10101 protein Q8WU94 942 CDNA FLJ14503 fis, clone Q96T17 NT2RM1000252, weakly similar to H. sapiens E-MAP-115 mRNA 943 E2F8 protein Q5BKY4 944 Human Hypothetical protein Q2VPJ3 945 HUMAN CDNA FLJ34154 fis, Q8NB70 clone FCBBF3013058 946 Hypothetical protein FLJ43654 Q6ZUJ4 (Hypothetical protein C3orf62) 947 HUMAN CDNA FLJ46180 fis, Q6ZRQ5 clone TESTI4004031 948 Flotillin-2 (Epidermal surface antigen) Q14254 (ESA) 949 Serine/threonine-protein kinase ATR Q13535 (EC 2.7.11.1) (Ataxia telangiectasia and Rad3-related protein) (FRAP-related protein 1) 950 Frizzled 5 precursor (Frizzled-5) Q13467 951 Fructose-bisphosphate aldolase C P09972 (EC 4.1.2.13) 952 G protein pathway suppressor 1 isoform Q53HS2 1 variant 953 KiSS-1 receptor (KiSS-1R) (Kisspeptins Q969F8 receptor) (Metastin receptor) (G-protein coupled receptor 54) 954 Probable G-protein coupled receptor 55 Q9Y2T6 955 Probable G-protein coupled receptor 35 Q9HC97 956 G-protein coupled receptor family C Q9NQ84 group 5 member C precursor (Retinoic acid-induced gene 3 protein) 957 Leucine-rich repeat-containing G-protein O75473 coupled receptor 5 precursor (Orphan G-protein coupled receptor HG38) (G-protein coupled receptor 49) (G-protein coupled receptor 67) 958 Probable G-protein coupled receptor 133 Q6QNK2 precursor (G-protein coupled receptor PGR25) 959 G1 to S phase transition protein 1 homolog P15170 (GTP-binding protein GST1-HS) 960 Gamma-aminobutyric-acid receptor alpha-6 Q16445 subunit precursor (GABA(A) receptor) 961 Ganglioside-induced differentiation- Q96MZ0 associated protein 1-like 1 (GDAP1-L1) 962 Gap junction alpha-5 protein P36382 (Connexin-40) (Cx40) 963 GEM-interacting protein (GMIP) Q9P107 964 Golgin subfamily B member 1 (Giantin) Q14789 965 UDP-N-acetylhexosamine pyrophosphorylase Q16222 (Antigen X) 966 Neutral alpha-glucosidase AB precursor Q14697 (EC 3.2.1.84) 967 Probable dolichyl pyrophosphate Q9BVK2 Glc1Man9GlcNAc2 alpha-1,3- glucosyltransferase (EC 2.4.1.—) 968 Bifunctional aminoacyl-tRNA synthetase P07814 [Includes: Glutamyl-tRNA synthetase (EC 6.1.1.17) (Glutamate--tRNA ligase); Prolyl-tRNA synthetase (EC 6.1.1.15) (Proline--tRNA ligase)] 969 Glycoprotein nmb-like protein Q8IXJ5 970 Prolactin-releasing peptide receptor P49683 (PrRP receptor) (PrRPR) (G-protein coupled receptor 10) 971 G protein-coupled receptor 112 Q5EGP2 972 Growth factor receptor-bound protein 14 Q14449 (GRB14 adapter protein) 973 GRIP and coiled-coil domain-containing Q8IWJ2 protein 2 (Golgi coiled coil protein GCC185) (CTCL tumor antigen se1-1) 974 GROS1-L protein Q9HC86 975 Growth hormone secretagogue receptor type 1 Q92847 (GHS-R) 976 Glutathione S-transferase A4-4 (EC 2.5.1.18) O15217 977 GTP-binding protein Rhes (Ras homolog Q96D21 enriched in striatum) (Tumor endothelial marker 2) 978 GTP-binding protein Rit1 (Ras-like protein Q92963 expressed in many tissues) 979 VGFG2573 Q6UY45 980 Hypothetical protein HDLBP Q53QU2 981 Heat shock protein 75 kDa, mitochondrial precursor (HSP75) (Tumor necrosis factor Q12931 type 1 receptor-associated protein) 982 Heat shock protein apg-1 Q53ZP9 983 Tumor rejection antigen (Gp96) 1 Q5CAQ5 984 Heat-shock protein beta-3 (HspB3) Q12988 (Heat shock 17 kDa protein) 985 Low-density lipoprotein receptor-related O75197 protein 5 precursor 986 Regulator of telomere elongation helicase 1 Q9NZ71 (EC 3.6.1.—) (Helicase-like protein NHL) 987 Hematopoietic protein 1 Q52LW0 988 Heme oxygenase 1 (EC 1.14.99.3) (HO-1) P09601 989 Heparan sulfate glucosamine 3-O- Q8IZT8 sulotransferase 5 (EC 2.8.2.23) 990 Hepatocellular carcinoma-associated antigen 66 Q9NYH9 991 Melanoma-associated antigen E2 Q8TD90 (MAGE-E2 antigen) (Hepatocellular carcinoma-associated protein 3) 992 26S proteasome non-ATPase regulatory O75832 subunit 10 (26S proteasome regulatory subunit p28) Hepatocellular carcinoma- associated protein p28-II 993 Hephaestin Q5JUU1 994 HECT domain and RCC1-like domain- O95714 containing protein 2 (HERC2) 995 Heteregeneous nuclear ribonucleoproteins P22626 A2/B1 (hnRNP A2/hnRNP B1) 996 Heteregeneous nuclear ribonuleoprotein R O43390 (hnRNP R) 997 HEXIM1 protein (HMBA-inducible) O94992 998 Histatin-1 precursor (Histidine-rich protein 1) P15515 999 Histone deacetylase 1 (HD1) Q13547 1000 Histone deacetlase 9 (HD9) (HD7B) (HD7) Q9UKV0 1001 Homeodomain-interacting protein kinase 2 Q9H2X6 (EC 2.7.11.1) 1002 Cullin-2 (CUL-2) Q13617 1003 SWI/SNF-related matrix-associated actin- O60264 dependent regulator of chromatin subfamily A member 5 (EC 3.6.1.—) 1004 HUMAN HPSC027 26S proteasome non-ATPase Q9Y6E3 regulatory subunit 13 Synonyms 26S proteasome regulatory subunit S11 26s proteasome regulatory subunit p40.5 1005 Hypothetical protein (Novel protein HSPC117) Q9Y3I0 (DJ149A16.6 protein) (Hypothetical protein HSPC117) 1006 Claudin domain-containing protein 1 Q9NY35 (Membrane protein GENX-3745) Q9NY35 1007 Large neutral amino acids transporter small Q9UHI5 subunit 2 (L-type amino acid transporter 2) (hLAT2) 1008 Heterogeneous nuclear ribonucleoprotein C-like 1 O60812 (hnRNP core protein C-like 1) 1009 Ornithine decarboxylase (EC 4.1.1.17) (ODC) P11926 1010 Regulator of nonsense transcripts 2 Q9HAU5 (Nonsense mRNA reducing factor 2) (Up-frameshift suppressor 2 homolog) (hUpf2) 1011 ATX10_HUMAN Ataxin-10 Q9UBB4 1012 KIAA1833 protein Q569G6 1013 HUMAN UDP-GalNAc:betaGlcNAc beta 1,3- Q8NCR0 galactosaminyltransferase, polypeptide 2 (Beta 1,3-N-acetylgalactosaminyltransferase-II) (MGC39558) 1014 Hypothetical protein KIAA1033 Q2M389 1015 Activating signal cointegrator 1 complex Q8N3C0 subunit 3 (EC 3.6.1.—) 1016 Delta-interacting protein A (Hepatitis delta Q15834 antigen-interacting protein A) Coiled-coil domain-containing protein 85B) 1017 Hypothetical protein HLJ14466 Q96BP7 1018 Interferon-inducible double stranded RNA- O75569 dependent protein kinase activator A 1019 Hypothetical protein C9orf142 Q9BUH6 1020 Tetratricopeptide repeat protein 17 Q96AE7 1021 CDNA FLJ14058 fis, clone HEMBB1000554 Q9H7Z0 1022 Anaphase promoting complex subunit 13 Q9BS18 1023 Hypothetical protein CCDC60 Q8IWA6 1024 Sphingosine kinase 2 (EC 2.7.1.—) Q9NRA0 1025 Probable ATP-dependent RNA helicase DDX11 Q96FC9 (EC 3.6.1.—) (DEAD/H box protein 11) (CHL1 homolog) (Keratinocyte growth factor-regulated gene 2 protein) (KRG-2) 1026 Protein KIAA0182 Q14687 1027 Ras GTPase-activitating protein SynGAP Q96PV0 (Synaptic Ras-GTPase-activating protein 1) (Synaptic Ras-GAP 1) (Neuronal RasGAP) 1028 Fibrinogen C domain containing 1 Q8N539 1029 MGC39581 protein Q86XM0 1030 Bcl-2-like 13 protein (Mil1 protein) (Bcl-rambo) Q9BXK5 1031 Myosin head domain containing 1 Q96H55 1032 WD-repeat protein 51A Q8NBT0 1033 KIF27A (OTTHUMP00000021559) Q86VH2 1034 Inositol polyphosphate-5-phosphatase F, Q2T9J4 isoform 1 1035 Myopalladin Q96KF5 1036 Rho GTPase activitating protein 12 Q5T2Y2 1037 Hypothetical protein DKFZp686D0630 Q7Z3C5 1038 Jumonji domain-containing protein 1C Q15652 (Thyroid receptor-interacting protein 8) (TRIP-8) 1039 Coatomer subunit beta (Beta-coat protein) P53618 (Beta-COP) 1040 FLJ10462 fis, clone NT2RP1001494, weakly Q9NVW8 similar to MALE STERILITY PROTEIN 2 1041 Cell-cycle and apoptosis regulatory protein 1 Q6X935 1042 Telomere-associated protein RIF1 Q5UIP0 (Rap1-interacting factor 1 homolog) 1043 F-box only protein 28 Q9NVF7 1044 CDNA FLJ10901 fis, clone NT2RP5003524 Q9NV65 1045 Acetoacetyl-CoA synthetase (EC 6.2.1.16) Q86V21 1046 Putative cell cycle control protein Q9NXZ0 (DEP domain containing 1) 1047 Synaptopodin 2-like Q68A20 1048 CDNA FLJ36560 fis, clone TRACH2009340 Q8N9T8 1049 CDNA FLJ13330 fis, clone OVAR1001802 Q9H8Q0 1050 ATP-dependent RNA helicase DDX31 Q9H8H2 (EC 3.6.1.—) DEAD box protein) (Helicain) 1051 Protein C14orf161 Q9Y4P1 1052 Cysteine protease ATG4B (EC 3.4.22.—) (Autophagy-related protein 4 homolog B) 1053 CDNA FLJ14526 fis, clone NT2RM1001139 Q96T08 1054 Hypothetical protein CCDC77 (CDNA Q9BR77 FLJ14732 fis, clone NT2RP3001969, weakly similar to TRICHOHYALIN) 1055 CDNA FLJ14790 fis, clone NT2RP4000973, Q96K38 weakly similar to PROBABLE PROTEIN DISULFIDE ISOMERASE P5 (EC 5.3.4.1) 1056 Keratin 24 Q2M2I5 1057 BCor protein (BCL-6 corepressor) Q6W2J9 1058 Hypothetical protein FLJ20582 Q6IQ21 1059 Hypothetical protein FLJ22688 Q9BT04 1060 Hypothetical protein FLJ22944 Q9H5W3 1061 Zinc finger protein, subfamily 1A, 5- Q8TBE5 1062 Leucine-rich repeats and IQ motif containing 2 Q8IW35 1063 Hypothetical protein FLJ23749 Q8TEA0 1064 Hypothetical protein FLJ25336 http://www.ex pasy.org/sprot/ userman.html - - AC_lineQ96L P1 1065 Hypothetical protein FLJ25660 Q8N7G6 1066 CDNA FLJ30058 fis, clone ADRGL2000074, Q96NU6 weakly to RHO-GTPASE-ACTIVATING PROTEIN 6 1067 CDNA FLJ30106 fis, clone BNGH41000190, Q96A82 weakly similar to Rattus norvegicus schlafen-4 (SLFN-4) mRNA. 1068 Whirlin Q9P202 1069 CDNA FLJ31846 fis, clone NT2RP7000425, Q96MV0 weakly similar to MYOSIN HEAVY CHAIN, NONMUSCLE TYPE B 1070 FLJ32833 fis, clone TESTI2003228 Q96M43 1071 Guanine nucleotide-binding protein G(olf), P38405 alpha subunit (Adenylate cyclase-stimulating G alpha protein, olfactory type) 1072 CDNA FLJ33811 fis, clone CTONG2002095 Q8N279 1073 Transmembrane protein 16C Q9BYT9 1074 Zinc finger protein 31 (Zinc finger protein P17040 KOX29) (Zinc finger and SCAN domain- containing protein 20) (Zinc finger protein 360) 1075 Transmembrane 6 superfamily member 2 Q9BZW4 1076 CDNA FLJ90251 fis, clone NT2RM4000115 Q8NCH3 1077 CDNA FLJ90760 fis, clone THYRO1000061 Q8N2I4 1078 Tubulin--tyrosine ligase-like protein 12 Q14166 1079 KIAA0303 protein O15021 1080 Plexin-B2 precursor (MM1) O15031 1081 Zinc finger and BTB domain-containing protein 5 O15062 1082 Centrosome-associated protein 350 Q8WY20 1083 piccolo (Aczonin) Q9Y6V0 1084 KIAA0560 protein O60306 1085 KIAA0676 protein Q96H49 1086 Human homolog of Mus SLIT and NTRK-like Q810B7 protein 5 precursor 1087 Nischarin Q6PIB4 1088 FERM domain-containing protein 4A Q9P2Q2 1089 Leucine-rich repeats neuronal protein 1 Q6UXK5 precursor (Neuronal leucine-rich repeat protein 1) (NLRR-1) 1090 KIAA1512 protein Q9P216 1091 KIAA1598 protein Q9HCH4 1092 Phosphatidylinositol-3 phosphate 3-phosphatase Q96QU2 adaptor subunit 1093 KIAA1730 protein Q9C0D3 1094 KIAA1786 protein Q96JN9 1095 Hypothetical protein MGC20470 Q96EK3 1096 OACT1 protein Q86XC2 1097 6-phosphofructo-2-kinase/fructose-2,6- Q16877 biphosphatase 4 (6PF-2-K/Fru-2,6-P2ASE testis-type isozyme) 1098 IkappaB kinase complex-associated protein O95163 (IKK complex-associated protein) (p150) 1099 Immune receptor expressed on myeloid Q7Z7I3 cells 2 1100 High-affinity cAMP-specific and IBMX- O60658 insensitive 3′,5′-cyclic phosphodiesterase 8A (EC 3.1.4.17) 1101 Bone specific CMF608 Q6WRI0 1102 Importin alpha-7 subunit (Karyopherin alpha-6) O60684 1103 InaD-like protein (Inadl protein) (hINADL) Q8NI35 (Pals1-associated tight junction protein) (Protein associated to tight junctions) 1104 Nitric oxide synthase, inducible (EC 1.14.13.39) P35228 1105 Transcription elongation factor SPT5 (hSPT5) O00267 1106 Inositol-trisphosphate 3-kinase B (EC 2.7.1.127) P27987 (Inositol 1,4,5-triphosphate 3-kinase B) 1107 Type I inositol-3,4-biphosphate 4-phosphatase Q96PE3 (EC 3.1.3.66) (Inositol polyphosphate 4- phosphatase type I) 1108 Insulin receptor beta subunit Q9UCB7 1109 Insulin-like growth factor binding protein, Q8TAY0 acid labile subunit 1110 Integrin beta-4 precursor (GP150) P16144 (CD104 antigen) 1111 Splice isoform 2 of P35462 P35462-2 1112 Interferon alpha 2 protein Q16055 1113 Interferon-induced protein with tetratricopeptide P09914 repeats 1 (IFIT-1) ) (Interferon-induced 56 kDa protein) (IFI-56K) 1114 Interleukin-20 precursor (IL-20) (Four alpha Q9NYY1 helix cytokine Zcyto10) 1115 Steroid receptor RNA activator isoform 1 Q9HD15 1116 Intersectin-2 (SH3 domain-containing protein 1B) (SH3P18) (SH3P18-like WASP-associated Q9NZM3 protein) 11117 ITI-like protein (Inter-alpha (Globulin) inhibitor Q6UXX5 H5-like) 1118 Gap junction alpha-5 protein (Connexin-40) P36382 1119 Kelch-like prolein 8 Q9P2G9 1120 Keratin, type II cytoskeletal 1 (Cylokeralin-1) P04264 1121 ADAM 9 precursor (EC 3.4.24.—) Q13443 (A disintegrin and metalloproteinase domain 9) (Metal loprotcase/disintegrin/cysteine-rich protein 9) (Myeloma cell metalloproleinase) 1122 Next to BRCA1 gene 1 protein (Neighbor of Q14596 BRCA1 gene1 protein) (Membrane component, chromosome 17, surface marker 2) (1A1-3B) 1123 Hypothetical protein DKFZp686K2075 Q6MZZ8 1124 KIAA0100 protein Q14667 1125 Pre-mRNA-splicing factor ATP-dependent RNA Q92620 helicase PRP16 (EC 3.6.1.—) (ATP-dependent RNA helicase DHX38) (DEAH box prolein 38) 1126 KIAA0251 protein Q8TBS5 1127 HUMAN KIAA0342 protein O15050 1128 KIAA0357 protein O15064 1129 Hypothetical protein KIAA0372 Q6PGP7 1130 KIAA0377 splice variant 2 Q86TE7 1131 KIAA0386 protein Q9Y4F9 1132 HUMAN CTCL tumor antigen HD-CL-04 Q548S1 1133 Importin-13 (Imp13) (Ran-binding protein 13) O94829 1134 KIAA0769 prolein O94868 1135 Hypothetical protein KIAA0863 Q6IQ32 1136 Zinc finger protein KIAA1196- Q96KM6 1137 CRSP complex subunit 3 (Cofactor required for Q9ULK4 Sp1 transcriptional activation subunit 3) (Transcriptional coactivator CRSP130) (Vitamin D3 receptor-interacting protein complex 130 kDa component 1138 [Pyruvate dehydrogenase [lipoamide]]- Q9P2J9 phosphatase 2, mitochondrial precursor (EC 3.1.3.43) 1139 Protocadherin-10 precursor Q9P2E7 1140 Leucine-rich repeats and calponin homology Q5VUJ6 (CH) domain containing 2 1141 Ankyrin repeat domain 18B Q5W0G2 1142 Kin17 protein (HsKin17 protein) (KIN, antigenic O60870 determinant of recA protein homolog) 1143 Kinesin-like protein KIF13A Q9H1H9 (Kinesin-like protein RBKIN) 1144 Putative RNA binding protein KOC O00425 1145 Keratin, type I cytoskeletal 18 (Cytokeratin-18) P05783 1146 Kv3.2d voltage-gated potassium channel Q86W09 1147 Lethal(3)malignant brain tumor-like protein Q9Y468 (L(3)mbt-like) (L(3)mbt protein homolog) 1148 Lactadherin precursor (Milk fat globule-EGF Q08431 factor 8) (MFG-E8) (HMFG) (Breast epithelial antigen BA46) (MFGM) 1149 Lamin-A/C (70 kDa lamin) P02545 1150 Laminin gamma-1 chain precursor P11047 (Laminin B2 chain) 1151 Low-density lipoprotein receptor-related O75197 protein 5 precursor 1152 Leptin receptor precursor (LEP-R) P48357 (OB receptor) 1153 Mitogen-aclivated protein kinase kinase O43283 kinase 13 (EC 2.7.11.25) 1154 Leukemia virus receptor 2 Q08357 1155 Leukemia-associated protein with a CXXC Q8NFU7 domain RNA-binding protein 6 (RNA-binding motif protein 6) 1156 (RNA-binding protein DEF-3) (Lung cancer P78332 antigen NY-LU-12) 1157 Lung cancer oncogene 5 Q7Z5Q7 1158 Heterogeneous nuclear ribonuclcoprotein M P52272 (hnRNP M) 1159 Macrophage migration inhibitory factor (MIF) P14174 (Phenylpyruvate lautomerase) (EC 5.3.2.1) 1160 Mitotic spindle assembly checkpoint protein Q9UI95 MAD2B (MAD2-like 2) (hREV7) 1161 Mitogen-activated protein kinase kinase kinase 4 Q9Y6R4 (EC 2.7.11.25) (MAPK/LRK kinase kinase 4) 1162 Serine/threonine/tyrosine-interacting-like Q9Y6J8 protein 1 (Dual-specificity protein phosphatase 24) (Map kinase phosphatase-like protein MK-STYX) 1163 Microtubule-associated serine/threonine-protein Q6P0Q8 kinase 2 (EC 2.7.11.1) 1164 Matrix metalloprotease MMP-27 Q9H306 1165 MCM10 protein Q7L590 1166 Interferon-induced helicase C domain-containing Q9BYX4 protein 1 (EC 3.6.1.—) (Melanoma differentiation-associated protein 5) 1167 Melanoma ubiquitous mutated protein Q2TAK8 1168 Melanoma antigen family D, 2 Q5BJF3 1169 Melanocyte protein Pmel 17 precursor P40967 (Melanocyte lineage-specific antigen GP100) 1170 GPI-anchored protein p137 (p137GPI) Q14444 (Membrane component chromosome 11 surface marker 1) Cytoplasmic activation/ proliferation-associated protein 1 1171 Hepatocyte growth factor receptor P08581 precursor (EC 2.7.10.1) (HGF receptor) (Scatter factor receptor) (SF receptor) (HGF/SF receptor) (Met proto-oncogene tyrosine kinase) 1172 Mitogen-activated protein kinase 14 Q16539 (EC 2.7.11.24) 1173 Mitogen-activated protein kinase kinase kinase Q12851 kinase 2 (EC 2.7.11.1) (MAPK/ERK kinase kinase kinase 2) 1174 Mitotic kinesin-relaled protein Q96Q89 1175 Sperm-associated antigen 5 (Astrin) (Mitotic Q96R06 spindle-associated protein p126) 1176 Myeloid/lymphoid or mixed-lineage leukemia Q9UMN6 protein 4 (Trithorax homolog 2) 1177 Putative helicase MOV-10 (EC 3.6.1.—) Q9HCE1 (Moloney leukemia virus 10 protein) 1178 MOZ/CBP protein Q712H6 1179 Calgranulin B (Migration inhibitory factor- P6702 related protein 14) (MRP-14) (P14) 1180 MUC2_HUMAN Mucin-2 precursor Q02817 (Intestinal mucin 2) 1181 Mucin-5B precursor (Mucin 5 subtype B, Q9HC84 tracheobronchial) 1182 Multiple PDZ domain protein O75970 (Multi PDZ domain protein 1) (Multi-PDZ-domain protein 1) 1183 RUFY2 (Run and FYVE domain-containing Q8IW33 protein Rabip4 1184 Multidrug resistance-associated protein 7 Q8NHX7 1185 Multiple copies in a T-cell malignancies Q9ULC4 (Malignant T cell amplified sequence 1) (MCT1) 1186 DNA mismatch repair protein Msh3 P20585 1187 Protein CBFA2T2 (MTG8-like protein) O43439 (MTG8-relaled protein 1) (Myeloid translocation-relaled protein 1) 1188 Myomesin-1 (190 kDa titin-associated protein) P52179 (190 kDa) connectin-associated protein 1189 Myosin heavy chain, cardiac muscle beta P12883 isoform (MyHC-beta) 1190 Myosin-13 (Myosin heavy chain, skeletal muscle, Q9UKX3 extraocular) (MyHC-eo) 1191 Tumor suppressor candidate 3 (N33 protein) Q13454 1192 Nebulin-related anchoring protein Q8TCH0 1193 Neural cell adhesion molecule 1, 1 PI3592 1194 Neurotrimin precursor Q9P121 1195 Ninein Q8N4C6 1196 Notch homolog 2 Q5VTD0 1197 Neurogenic locus notch homolog protein 1 P46531 precursor (Notch 1) (hN1) (Translocation- associated notch protein TAN-1) [Contains: Notch 1 extracellular truncation; Notch 1 intracellular domain] 1198 Neurogenic locus notch homolog protein 3 Q9UM47 precursor (Notch 3) [Contains: Notch 3 extracellular truncation; Notch 3 intracellular domain ] 1199 Neurogenic locus notch homolog protein 4 Q99466 precursor (Notch 4) (hNotch4) [Contains: Notch 4 extracellular truncation; Notch 4 intracellular domain]- 1200 Plexin-A1 precursor (Semaphorin receptor NOV) Q9UIW2 1201 HUMAN NPD011 Q9H2R7 1202 Nuclear autoantigen Sp-100 (Speckled 100 kDa) P23497 (Nuclear dot-associated Sp100 protein) 1203 Nuclear factor erythroid 2-related factor 1 (NF- Q14494 E2-related factor 1) (NFE-2-related factor 1) (Nuclear factor, erythroid derived 2, like 1) (Transcription factor 11) (Transcription factor HBZ17) (Transcription factor LCR-F1) (Locus control region-factor 1) 1204 Nuclear factor of activated T-cells, cytoplasmic 1 O95644 (NFAT transcription complex cytosolic component) (NF-ATc1) 1205 Nuclear receptor coactivator 2 (NCoA-2) Q15596 (Transcriptional intermediary factor 2) 1206 Ubiquitin-like PHD and RING finger domain- Q96T88 containing protein 1 (EC 6.3.2.—) 1207 Nucleic acid helicase DDXx Q8IWW2 1208 Nucleoporin 62 kDa (NUP62 protein) Q6GTM2 1209 Nuclear pore complex protein Nup98-Nup96 P52948 precursor [Contains: Nuclear pore complex protein Nup98 (Nucleoporin Nup98) (98 kDa nucleoporin); 1210 Nucleoprotein TPR P12270 1211 Nuclear pore complex protein Nup107 P57740 1212 Nuclear pore complex protein Nup205 Q92621 1213 ODF2 protein QAPJQ8 1214 Trophoblast glycoprotein precursor Q13641 (5T4 oncofetal trophoblast glycoprotein) 1215 Dynamin-like 120 kDa protein, mitochondrial O60313 precursor (Optic atrophy 1 gene protein) 1216 Orexin receptor type 2 (Ox2r) (Hypocretin O43614 receptor type 2) 1217 Transmembrane emp24 domain-containing P49755 protein 10 precursor (Transmembrane protein Tmp21) 1218 Orphan nuclear receptor TR2 (Testicular P13056 receptor 2) 1219 MKL/myocardin-like protein 1 (Myocardin- Q969V6 related transcription factor A) (MRTF-A) (Megakaryoblastic leukemia 1 protein) (Megacaryocytic acute leukemia protein) 1220 Ovarian cancer related tumor marker CA125- Q8WXI7 1221 Oxysterol-binding protein-related protein 8 Q9BZF1 (OSBP-related protein 8) 1222 Centrosomal protein of 70 kDa (Cep70 protein) Q8NHQ1 (p10-binding protein) 1223 Leucine carboxyl methyl transferase 2 O60294 (EC 2.1.1.—) (p21WAF1/CIP1 promoter- interacting protein) 1224 F-box/LRR-repeat protein 5 (F-box and Q9UKAJ leucine-rich repeat protein 5) (F-box protein FBL4/FBL5) 1225 Inhibitor of growth protein 3 Q9NXR8 1226 P53 inducible protein Q9UN29 1227 DNA polymerase alpha catalytic subunit P09884 (EC 2.7.7.7) 1228 Chloride intracellular channel protein 4 Q9Y696 (Intracellular chloride ion channel protein p64H1 1229 Paired mesoderm homeobox protein 2B (Paired- Q99453 like homeobox 2B) (PXOX2B homeodomain protein) (Neuroblastoma Phox) 1230 PRB3 protein P81489 1231 Protein patched homolog 1 (PTC1) (PTC) Q13635 1232 Rap guanine nucleotide exchange factor 2 Q9Y4G8 (Neural RAP guanine nucleotide exchange protein) (nRap GEP) (PDZ domain-containing guanine nucleotide exchange factor 1) (PDZ-GEF1) 1233 Pecanex-likc protein 1 (Pecanex homolog)- Q96RV3 1234 GC-1-related estrogen receptor alpha coactivator Q8TDK4 short isoform 1235 PHD finger Q86U89 1236 Hypothetical protein DKFZp686C07187 Q6N038 1237 Phosphalidylinositol-4,5-bisphosphate 3-kinase P42338 catalytic subunit beta isoform (EC 2.7.1.153) (PI3-kinase p110 subunit beta) (PtdIns-3-kinase p110) 1238 Phosphodiesterase 8A, isoform 1 Q6P9H3 1239 Serine/threonine-protein kinase SMG1 Q96Q15 (EC 2.7.11.1) (SMG-1) (hSMG-1) (Lambda/iota protein kinase C-interacting protein) (Lambda- interacting protein) ( 1240 PiggyBac transposable element derived 3 Q8N328 1241 PIWIL protein Q7Z3Z3 1242 Homeobox protein PKNOX1 (PBX/knotted P55347 homeobox 1) 1243 Transmembrane protein 115 (Protein PL6) Q12893 1244 Plakophilin-2 Q99959 1245 Plectin 6 Q6S380 1246 Plectin 1 (PLTN) (PCN) Q15149 (Hemidesmosomal protein 1) (HD1) O43157 1247 Plexin B1; plexin 5; semaphorin receptor 1248 Pleiotropic regulator 1 O43660 1249 Blood vessel epicardial substance (hBVES) Q8NE79 (Popeye domain-containing protein 1) (Popeye protein 1) 1250 Carboxypeptidase-like protein X2 precursor Q8N436 1251 YIF1B protein Q5BJH7 1252 Melanoma antigen preferentially expressed in P78395 tumors (Pr4eferentially expressed antigen of melanoma) (OPA-interacting protein 4) 1253 Splice isoform 2 of Q9H7F0 Q9H7F0-2 1254 P2Y purinoceptor 13 (P2Y13) (G-protein coupled Q9BPV8 receptor 86) (G-protein coupled receptor 94) 1255 Putative pre-mRNA-splicing factor ATP- O43143 dependent RNA helicase DHX15 (EC 3.6.1.—) (DEAH box protein 15) (ATP-dependent RNA helicase #46) 1256 HUMAN RNA-binding protein 34 (RNA-binding P42696 motif protein 34) 1257 Prolyl 4-hydroxylase alpha-1 subunit precursor (EC 1.14.11.2) (4-PH alpha-1) (Procollagen- P13674 proline,2-oxoglutarate-4-dioxygenase alpha-1 subunit) 1258 Profilin-1 P07737 1259 Programmed cell death protein 5 (TEAR 19 O14737 protein) (TF-1 cell apoptosis-related gene 19 protein) 1260 Propionyl-CoA carboxylase beta chain, P05166 mitochondrial precursor (EC 6.4.1.3) 1261 26S proteasome non-ATPase regulatory Q99460 subunit 1 (26S proteasome regulatory subunit RPN2) (26S proteasome regulatory subunit S1) (26S proleasome subunit p112) 1262 26S proteasome non-ATPase regulatory subunit 3 O43242 (26S proteasome regulatory subunit S3) (Proteasome subunit p58) 1263 Proteasome activator complex subunit 3 P61289 (Proteasome activator 28-gamma subunit) (PA28gamma) (PA28g) (Activator of multicatalytic protease subunit 3) (11S regulator complex gamma subunit) (RFG-gamma) (Ki nuclear autoantigen) 1264 Protein C14orf166 Q9Y224 1265 Protein KIAA1219 Q86X10 1266 Protein KIAA1688 Q9C0H5 1267 Protein Plunc precursor (Palate lung and nasal Q9NP55 epithelium clone protein) (Lung-specific protein X) (Nasopharyngeal carcinoma-related protein) (Tracheal epithelium-enriched protein) (Secretory protein in upper respiratory tracts) 1268 Protein transport protein Sec23B Q15437 1269 Liprin-alpha-2 (Protein tyrosine phosphatase O75334 receptor type f polypeptide-interacting protein alpha-2) (PTPRF-interacting protein alpha-2) 1270 Protocadherin gamma A12 precursor (PCDH- O60330 gamma-A12) (Cadherin-21) (Fibroblast cadherin 3) 1271 Protocadherin gamma A10 precursor (PCDH- Q9Y5H3 gamma-A10) 1272 Leucine carboxyl methyltransferase 2 O60294 (EC 2.1.1.—) (p21WAF1/CIP1 promoter- interacting protein) 1273 KIAA1636 protein Q9HCD6 1274 Probable G-protein coupled receptor 160 Q9UJ42 1275 Protein C21orf45 Q9NYP9 1276 Periodic tryptophan protein 2 homolog Q15269 1277 Rab-like protein 2B Q9UNT1 1278 Cell cycle checkpoint protein RAD17 (hRad17) O75943 (RF-C/activator 1 homolog) 1279 DNA repair protein RAD50 (EC 3.6.—.—) Q92878 (hRAD50) 1280 Ras GTPase-activating protein 1 (GTPase- P20936 activating protein) (GAP) (Ras p21 protein activator) (p120GAP) (RasGAP) 1281 Ras guanine nucleotide exchange factor 2 Q9UK56 1282 Ras-GTPase-activating protein-binding protein 1 Q13283 (EC 3.6.1.—) (ATP-dependent DNA helicase VIII) (GAP SH3-domain-binding protein 1) (G3BP-1) (HDH-VIII) 1283 Ras-related protein Rab-27A (Rab-27) (GTP- P51159 binding protein Ram) 1284 Ras-related protein Rab-3D O95716 1285 Nuclear pore complex protein Nup107 P57740 (Nucleoporin Nup107) (107 kDa nucleoporin) 1286 Receptor-interacting factor 1 Q86XS4 1287 Regulating synaptic membrane exocytosis protein Q9UJD0 3 (Nim3) (Rab-3 interacting molecule 3) (RIM 3) (RIM3 gamma) 1288 Regulator of G protein signaling protein Q86UV0 (Regulator of G-protein signalling like 1) 1289 MHC class II regulatory factor RFX1 (RFX) P22670 (Enhancer factor C) (EF-C) 1290 Retinoblastoma-associated protein (PP110) P06400 (P105-RB) 1291 Roundabout homolog 3 precursor (Roundabout- Q96MS0 like protein 3) 1292 Retinoblastoma-associated protein HEC O14777 (Kinetochore associated 2) 1293 Retinoblastoma-associated protein RAP140 Q9UK61 1294 AT-rich interactive domain-containing protein P29374 4A (ARID domain-containing protein 4A) (Retinoblastoma-binding protein 1) 1295 Jumonji/AKID domain-containing protein 1A P29375 (Retinoblastoma-binding protein 2) (RBBP-2) 1296 RhoGTPase regulating protein variant Q6RJU5 ARHGAP20-1ad 1297 40S ribosomal protein S4, Y isoform 2 Q8TD47 1298 RNA binding motif Q13380 1299 RNA binding protein (Autoantigenic, hnRNP- Q2M365 associated with lethal yellow), long isoform - 1300 RNA-binding protein Q8NI52 1301 Ro ribonucleoprotein-binding protein 1 Q9UHX1 (SIAHBP1 protein) 1302 HUMAN OTTHUMP00000030902 Q5JYR6 1303 Ryanodine receptor 2 (Cardiac muscle-type Q92736 ryanodine receptor) (RyR2) (RYR-2) (Cardiac muscle ryanodine receptor-calcium release channel) (hRYR-2) 1304 SEC14-like protein 1 Q92503 1305 Secreted and transmembrane protein 1 precursor Q8WVN6 (Protein K12) 1306 Neudesin precursor (Neuron-derived Q9UMX5 neurotrophic factor) 1307 P-selectin glycoprotein ligand 1 precursor Q14242 (PSGL-1) (Selectin P ligand) (CD162 antigen) 1308 Semaphorin-6D precursor Q8NFY4 1309 Serine/threonine/tyrosine-interacting protein Q8WUJ0 (Protein tyrosine phosphatase-like protein) 1310 Olfactory receptor 8G5 (Olfactory receptor Q8NG78 OR11-298) 1311 Shb-likc adapter protein, Shf Q7M4L6 1312 Signal transducer and activator of transcription P42224 1-alpha/beta (Transcription factor ISGF-3 components p91/p84) STAT1 1313 Signal transducer and activator of transcription 3 P40763 (Acute-phase response factor) 1314 40S ribosomal protein S7 P62081 1315 60S ribosomal protein L35 P42766 1316 60S ribosomal protein L7 P18124 1317 Thrombospondin-2 precursor P35442 1318 C3 and PZP-like alpha-2-macroglobulin Q8IZJ3 domain containing 8 1319 ATP-binding cassette sub-family F member 2 Q9UG63 (Iron-inhibited ABC transporter 2) 1320 Ribosome biogenesis protein BOP1 (Block of Q14137 proliferation 1 protein) 1321 CDNA FLJ13765 fis, clone PLACE4000128, Q9H8C5 weakly similar to Mus musculus putative transcription factor mRNA 1322 CD200 cell surface glycoprotein receptor Q6Q8B3 isoform 2 variant 2 1323 LRRC58 protein Q96CX6 1324 Claudin-6 (Skullin 2) P56747 1325 T-box transcription factor TBX18 O95935 (T-box protein 18) 1326 INTS7 protein Q8WUH5 1327 FRAS1-related extracellular matrix protein 2 Q5SZK8 precursor (ECM3 homolog) 1328 Zinc finger protein 318 (Endocrine regulatory Q5VUA4 protein) 1329 Eukaryotic translation initiation factor 3 subunit Q99613 8 (eIF3 p110) (eIF3c) 1330 HUMAN LOC196394 protein Q8IY45 1331 Hypothetical protein FLJ44216 Q8NDZ2 1332 Heat shock protein HSP 90-beta (HSP 84) P08238 (HSP 90) 1333 Sarcoma antigen NY-SAR-41 (NY-SAR 41) Q5T9S5 1334 Protein FAM86A Q96G04 1335 Ras-like family 11 member A Q6T310 (OTTHUMP00000018162) 1336 Keratin, type I cytoskeletal 18 (Cytokeratin-18) P05783 (CK-18) 1337 U3 small nucleolar RNA-associated protein Q9BVJ6 14 homolog A (Antigen NY-CO-16) 1338 Hypothetical protein DKFZp781D1722 Q68DM0 1339 Chromosome-associated kinesin KIF4A O95239 (Chromokinesin) 1340 Kinesin-like protein KIF6 Q6ZMV9 1341 Myosin-10 (Myosin heavy chain, nonmuscle IIb) P35580 (Nonmuscle myosin heavy chain IIb) 1342 Hypothetical protein C17orf57 Q8IY85 1343 Similar to peptide N-glycanase homolog Q9BVR8 (S.cerevisiae) 1344 Peptidyl-prolyl cis-trans isomerase A P62937 (EC 5.2.1.8) 1345 Serpin A13 precursor Q6UXR4 1346 40S ribosomal protein SA (p40) (34/67 kDa P08865 laminin receptor) (Colon carcinoma laminin- binding protein) (NEM/1CHD4) (Multidrug resistance-associated protein MGr1-Ag) 1347 N-acetylglucosamine-1-phosphotransferase Q9UJJ9 subunit gamma precursor 1348 Liprin-beta-1 (Protein tyrosine phosphatase Q86W92 receptor type f polypeptide-interacting protein- binding protein 1) 1349 40S ribosomal protein S3a P61247 1350 40S ribosomal protein S3a P61247 1351 LOC124512 protein (Fragment) Q86XA0 1532 Hypothetical protein MGC26744 Q96KX1 1535 Hypothetical protein LOC122258 Q96KW9 1354 Sulfiredoxin-1 (EC 1.8.98.2) Q9BYN0 1355 Basalin Q5QJ38 1356 Protein FAM86A Q96G04 1357 Transmembrane protein 16F Q4KMQ2 1358 TEB4 protein O14670 1359 SLC10A5 Q5PT55 1360 Serine/threonine-protein kinase SNF1-like P57059 kinase 1 (EC 2.7.11.1) 1361 LOC391257 protein Q6P094 1362 Zinc finger protein 161 (Putative transcription Q14119 factor DB1) 1363 Slit homolog 2 protein precursor (Slit-2) O94813 1364 FYN-binding protein (FYN-T-binding protein) O15117 1365 Jumonji/ARID domain-containing protein 1C P41229 (SmcX protein) (Xe169 protein) 1366 Jumonji/ARID domain-containing protein 1D Q9BY66 (SmcY protein) (Histocompatibility Y antigen) 1367 Monocarboxylate transporter 3 (MCT 3) O95907 1368 Solute carrier family 4 sodium bicarbonate Q6U841 cotransporter-like member 10- 1369 Sorting nexin 14, isoform a Q6NUI7 1370 Sorting nexin-4 O95219 1371 Spectrin beta chain, brain 4 Q9NRC6 (Spectrin, non-erythroid beta chain 4) 1372 Spermatogenesis-associated protein 7 Q9P0W8 (Spermatogenesis-associated protein HSD3) 1373 Non-POU domain-containing octamer- Q15233 binding protein (NonO protein) (54 kDa nuclear RNA- and DNA-binding protein) (p54(nrb) (p54nrb) (55 kDa nuclear protein) 1374 Cohesin subunit SA-1 (Stromal antigen 1) Q8WVM7 (SCC3 homolog 1) 1375 Steroid receptor RNA activator isoform 1 Q9HD15 1376 Structure-specific recognition protein 1 (SSRP1) (Recombination signal sequence recognition Q08945 protein) (T160) (Chromatin-specific transcription elongation factor 80 kDa subunit) 1377 Suppressor of hairy wing homolog 2 (5′OY11.1) Q86YH2 (Zinc finger protein 632) 1378 Transcription elongation factor SPT5 (hSPT5) O00267 (DRB sensitivity-inducing factor large subunit) (DSIF large subunit) (DSIFp160) (Tat- cotransactivator 1 protein) (Tat-CT1 protein)- 1379 Synaptogyrin-3 O43761 1380 Synaptojanin-2-binding protein (Mitochondrial P57105 outer membrane protein 25) 1381 Synemi Q8TE61 1382 Talin-1 Q9Y490 1383 TAR RNA loop binding protein Q13395 (TAR (HIV) RNA binding protein 1) 1384 Taste receptor type 2 member 3 (T2R3) Q9NYW6 1385 Taste receptor type 2 member 40 (T2R40) P59535 (T2R58) (G-protein coupled receptor 60) 1386 Oxidoreductase HTATIP2 (HC 1.1.1.—) Q9BUP3 (HIV-1 TAT-interactive protein 2) 1387 Transcription initiation factor TFIID subunit 6 P49848 (Transcription initiation factor TFIID 70 kDa subunit) (TAF(II)70) (TAFII-70) (TAFII-80) (TAFII80) 1388 TRA@ protein Q6PIP7 1389 T-complex protein 1 subunit beta (TCP-1-beta) P78371 (CCT-beta) 1390 Telomerase-binding protein EST1A (Ever shorter Q86US8 telomeres 1A) (Telomerase subunit EST1A) (EST1-like protein A) (hSmg5/7a) 1391 Tumor endothelial marker 6 (Hypothetical protein Q96PE0 TEM6) 1392 Ras GTPase-activating-like protein IQGAP2 Q13576 1393 Tetratricopeptide repeal protein 15 Q8WVT3 (TPR repeat protein 15) 1394 Myosin-18A (Myosin XVIIIa) (Myosin Q92614 containing PDZ domain) (Molecule associated with JAK3 N-terminus) (MAJN) 1395 Polycystic kidney and hepatic disease 1 Q8TCZ9 precursor (Fibrocyslin) 1396 TMC4 protein Q7Z5M3 1397 MDC-3.13 isolorm 1 (TNFAIP8 protein) Q9UER5 1398 Toll-like receptor 8 precursor Q9NR97 1399 Tolloid-like protein 1 precursor (EC 3.4.24.—) O43897 1400 DNA topoisomerase I, mitochondrial precursor Q969P6 (EC 5.99.1.2) (TOP1mt) 1401 PAP associated domain-containing protein 5 Q8NDF8 (EC 2.7.7.—) (Topoisomerase-related function protein 4-2) (TRF4-2) 1402 Plastin-3 (T-plastin) P13797 1403 Translocated promoter region Q5SWY0 (To activated MET oncogene) 1404 P2Y purinoceptor 13 (P2Y13) (G-protein Q9BPV8 coupled receptor 86) (G-protein coupled receptor 94) 1405 Transcript Y 5 Q9BXH6 1406 Transcription factor Sp4 (SPR-1) Q02446 1407 Transcription initiation factor TFIID subunit 1 P21675 (EC 2.7.11.1) (Transcription initiation factor TFIID 250 kDa subunit) (TAF(II)250) (TAFII-250) (TAFII250) (TBP-associated factor 250 kDa) (p250) (Cell cycle gene 1 protein) 1408 Transcriptional repressor CTCFL (CCCTC- Q8NI51 binding factor) (Brother of the regulator of imprinted sites) (Zinc finger protein CTCF-T) (CTCF paralog 1409 Transducer of regulated CREB protein 3 Q6UUV7 1410 Transmembrane channel-like protein 4 Q7Z404 1411 Transcription initiation factor TFIID subunit 6 P49848 (Transcription initiation factor TFIID 70 kDa subunit) (TAF(II)70) (TAFII-70) (TAFII-80) (TAFII80) 1412 Trophinin-associated protein (Tastin) Q12815 (Trophinin-assisting protein) 1413 Tryptophanyl-tRNA synthetase (EC 6.1.1.2) P23381 (Tryptophan--tRNA ligase) (TrpRS) (IFP53) (hWRS) 1414 Tubulin, gamma complex associated protein 3 Q5T9Y2 1415 Tumor necrosis factor ligand superfamily member 6 (Fas antigen ligand) (Fas ligand) (CD178 antigen) P48023 (CD95L protein) (Apoptosis antigen ligand) (APTL) [Contains: Tumor necrosis factor ligand superfamily member 6, membrane form 1416 Tumor necrosis factor, alpha-induced protein 1, Q13829 endothelial (B12 protein) 1417 Netrin receptor DCC precursor (Tumor suppressor P43146 protein DCC) (Colorectal cancer suppressor) 1418 Adipocyte-derived leucine aminopeptidase Q9NZ08 precursor (EC 3.4.11.—) (A-LAP) (ARTS-1) (Aminopeptidase PILS) (Puromycin-insensitive leucyl-specific aminopeptidase) (PILS-AP) (Type 1 tumor necrosis factor receptor shedding aminopeptidase 1419 U1 small nuclear ribonucleoprotein A P09012 (U1 snRNP protein A) (U1A protein) (U1-A 1420 U6 snRNA-associatcd Sm-like protein LSm8 O95777 1421 Ubiquitin-protein ligase E3A (KC 6.3.2.—) Q05086 (E6AP ubiquilin-protein ligase) (Oncogenic protein-associated protein E6-AP) (Human papillomavirus E6-associated protein) 1422 Ubiquitin carboxyl-terminal hydrolase 3 Q9Y6I4 (EC 3.1.2.15) (Ubiquitin thioesterase 3) (Ubiquitin-specific-processing protease 3) (Deubiquitinating enzyme 3) 1423 UBX domain-containing protein 2 Q92575 1424 UNC93 homolog B1 (UNC-93B protein) Q9H1C4 (hUNC93B1) 1425 Splice isoform 5 of Q9H171 Q9H171-5 1426 CDNA FLJ46282 fis, clone TESTI4031066 Q6ZRK6 1427 CCDC73 protein Q6P5Q7 1428 Caspase recruitment domain-containing protein 10 Q9BWT7 (CARD-containing MACUK protein 3) (Carma 3) 1429 Chromatin-specific transcription elongation Q9Y5B9 factor FACT 140 kDa subunit 1430 Beta-defensin 120 precursor Q8N689 1431 Alpha-catulin (Catenin alpha-like protein 1) Q9UBT7 (Alpha-catenin-related protein) 1432 Ribonuclease III (EC 3.1.26.3) (RNase III) Q9NRR4 1433 Seizure related 6 homolog Q53EL9 1434 Granulocyte colony-stimulating factor precursor P09919 (G-CSF) (Pluripoietin) (Filgrastim) (Lenograstim) 1435 Lysyl-tRNA synthetase Q9HB23 1436 Protein C6orf130 Q9Y530 1437 Melanophilin (Exophilin-3) (Synaptotagmin-like Q9BV36 protein 2a) (Slp homolog lacking C2 domains a) 1438 Novel protein (Possible ortholog of mouse Q5VTR6 phosphoinositide-3-kinase adaptor protein 1 (Pik3ap1) 1439 AHR61 glycosyltransferase Q6P985 1440 Heat shock protein HSP 90-alpha (HSP 86) P07900 1441 60S ribosomal protein L19 P84098 1442 PDZ domain-containing protein 11 Q5EBL8 1443 Dedicator of cytokinesis 11-; Cdc42- associated guanine nucleotide exchange factor ACG/DOCK11 Q5JSL3 1444 Hypothetical protein FLJ26930 Q6ZNX6 1445 Laminin gamma-1 chain precursor P11047 (Laminin B2 chain) 1446 ATP-binding cassette transporter sub-family Q96J66 C member 11 (Multidrug resistance- associated protein 8) 1447 Uridine/cytidine kinase-like 1 Q9NWZ5 1448 Butyrophilin-like protein 8 precursor Q6UX41 1449 Endothelial cell-selective adhesion molecule Q96AP7 precursor 1450 Poly(A)-specific ribonuclease PARN O95453 (EC 3.1.13.4) (Polyadenylale-specific ribonuclease) (Deadenylating nuclease) (Deadenylation nuclease) 1451 Voltage-gated potassium channel KCNA7 Q96RP8 1452 F-box protein 11 Q52ZP1 1453 rythrocyte membrane protein band 4.1 like 5 Q7Z5S1 1454 CDNA FLJ45015 fis, clone BRAWH3014639 Q6ZT30 1455 FAM13A1_v2 protein Q24JP0 1456 Hypothetical protein FLJ26432 Q6ZP70 1457 VPS13D-1A protein Q709C5 1458 Coagulation factor VIII precursor P00451 (Procoagulant component) (Antihemophilic factor) (AHF) 1459 NFX1-type zinc finger-containing protein 1 Q9P2E3 1460 Polymerase I and transcript release factor Q6NZI2 (PTRF protein) 1461 T-complex protein 1 subunit epsilon P48643 (TCP-1-epsilon) (CCT-epsilon) 1462 Probable ATP-dependent RNA helicase DDX27 Q96GQ7 (EC 3.6.1.—) (DEAD box protein 27) 1463 HSCARG Q9HBL8 1464 CDNA FLJ43956 fis. clone TESTI4015681 Q6ZU72 1465 Mitochondrial-processing peptidase alpha Q10713 subunit, mitochondrial precursor (EC 3.4.24.64) (Alpha-MPP) 1466 CDNA FLJ45287 fis, clone BRHIP3002124 Q6ZSK0 1467 Hypothetical protein C12orf62 Q96I36 1468 VPS13D-2A protein Q709C4 1469 CDNA FLJ32009 fis, clone NT2RP7009498, Q96DN2 weakly similar to FIBUUN-1, ISOFORM A 1470 Transient receptor potential cation channel Q9HBA0 subfamily V member 4 (TrpV4) (osm-9-like TRP channel 4) (OTRPC4) (Vanilloid receptor-like channel 2) (Vanilloid receptor-like protein 2) (VRL-2) 1471 Vascular endothelial growth factor D O43915 precursor (VFGF-D) (c-fos-induced growth factor) (FIGF) 1472 Vascular endothelial growth factor receptor 1 P17948 precursor (EC 2.7.10.1) (VFGFR-1) (Vascular permeability factor receptor) (Tyrosine-protein kinase receptor FLT) (Flt-1) (Tyrosine-protein kinase FRT) (Fms-like tyrosine kinase 1) 1473 Proto-oncogene C-crk (P38) (Adapter molecule crk) P46108 1474 VDUP1 protein (Thioredoxin interacting protein) Q9H3M7 1475 Vimentin P08670 1476 HUMAN CTCL tumor antigen HD-CL-06 Q548L2 (Vimentin variant) 1477 Vinculin (Metavinculin) P18206 1478 Integrin alpha-3 precursor (Galaetoprotein B3) P26006 (GAPB3) (VLA-3 alpha chain) (FRP-2) (CD49c antigen) [Contains: Integrin alpha-3 heavy chain; Integrin alpha-3 light chain] 1479 Voltage-dependent T-type calcium channel alpha-1H subunit (Voltage-gated calcium O95180 channel alpha subunit Cav3.2) (Low-voltage- activated calcium channel alpha1 3.2 subunit) 1480 Wiskott-Aldrich syndrome protein family Q8IV90 member 4 (WASP-family protein member 4) 1481 ATP synthase coupling factor 6, mitochondrial P18859 precursor (EC 3.6.3.14) (ATPase subunit F6) 1482 Proto-oncogene protein Wnt-3 precursor P56703 1483 Amyloid beta A4 precursor protein-binding Q99767 family A member 2 (Neuron-specific X11L protein) (Neuronal Munc18-1-interacting protein 2) (Mint-2) (Adapter protein X11beta) 1484 Zinc finger CCHC domain-containing protein 5 Q8N8U3 1485 Myeloid/lymphoid or mixed-lineage leukemia Q59FF2 (Trithorax homolog, Drosophila) variant 1486 Zinc finger protein DZIP1 Q86YF9 (DAZ-interacting protein 1/2) 1487 Hypothetical protein DKFZp761O1618 Q69YS5 1488 ATP-binding cassette sub-family F member 2 Q9UG63 (Iron-inhibited ABC transporter 2) 1489 Ribosome biogenesis protein BOP1 Q14137 (Block of proliferation 1 protein) 1490 CDNA FLJ13765 fis, clone PLACE4000128 Q9H8C5 1491 NDRG1 protein (N-myc downstream Q92597 regulated gene 1 protein) 1492 Pre-mRNA splicing factor ATP-dependent Q92620 RNA helicase PRP16 1493 Nesprin 2 (Nuclear envelope spectrin Q9NU50 repeat protein 2) 1494 Adenomatous polyposis coli P25054 1495 Ubiquitin conjugating enzyme E2 P49459 1496 B cell receptor-associated protein BAP31 P5572 (CDM protein) 6c6-AG 1497 Topoisomerase II-alpha P11388 1498 Topoisomerase II beta Q02880 1499 Integrin beta8 subunit precursor P26012 1500 Replication Protein A P27694 1501 Abl Binding protein 3 U31089 1502 Cyclin I Q14094 1503 Cell Division Control Protein 2 (CDC2) P06493 1504 Septin 2 (NEDD5) Q15019 1505 STAT1 alpha/beta P42224 1506 LDL Receptor-related protein (LRP) Q07954 1507 TACE (ADAM 17) NP-068604 1508 Junction plakoglobin (gamma catenin) P14923 1509 EDDR1 Q08345 1510 IP3 receptor type II Q14571 1511 Melanoma-associated antigen D2 (MAGE-D2 antigen) (MAGE-D) (Breast cancer-associated Q9UNF1 gene 1 protein) (BCG-1) (11B6) (Hepatocellular carcinoma-associated protein JCL-1) 1512 Melanoma-associated antigen 4 (MAGE-4 P43358 antigen) (MAGE-X2) (MAGE-41) 1513 HUMAN Retinoblastoma-like protein 2 Q08999 (130 kDa retinoblastoma-associated protein) (PRB2) (P130) (RBR-2)
Claims (17)
1. A method for eliciting a CTL response against tumor cells presenting at least one of the following epitopic peptides: SEQ ID NO: 1516, 1517, 1519, 1521, 1527, 1528, or 1529 in a subject, comprising administering to said subject a composition comprising
at least one polypeptide comprising an epitopic peptide comprising an amino acid sequence selected from the group consisting of SEQ ID NO: 1516, 1517, 1519, 1521, 1527, 1528, and 1529 in an amount sufficient to induce a CTL response to said tumor cells; or
at least one polypeptide comprising an epitopic peptide having no more than one amino acid difference from an amino acid sequence selected from the group consisting of SEQ ID NO: 1516, 1517, 1519, 1521, 1527, 1528, and 1529 in an amount sufficient to induce a CTL response to said tumor cells.
2. The method of claim 1 , wherein said amino acid difference is the result of a conservative amino acid substitution.
3. The method of claim 1 , wherein said amino acid difference is the result of a substitution of one hydrophobic amino acid with another hydrophobic amino acid.
4. The method of claim 1 , wherein said amino acid difference is the result of an addition or deletion of one amino acid to or from said epitopic peptide.
5. The method of claim 1 , wherein said composition further comprises an adjuvant.
6. The method of claim 5 , wherein said adjuvant is selected from the group consisting of complete Freund's adjuvant, incomplete Freund's adjuvant, Montanide ISA-51, LAG-3, aluminum phosphate, aluminum hydroxide, alum, and saponin.
7. The method of claim 1 , wherein said composition further comprises a cytokine.
8. The method of claim 7 , wherein said cytokine is GM-CSF.
9. The method of claim 1 , wherein said composition further comprises a vehicle.
10. The method of claim 9 , where said vehicle is selected from the group consisting of a liposome, an immunostimulating complex (ISCOM), and slow-releasing particles.
11. The method of claim 10 , wherein said liposome comprises an emulsion, a foam, a micelle, an insoluble monolayer, a liquid crystal, a phospholipid dispersion, or a lamellar layer.
12. The method of claim 1 , wherein said polypeptide consists of
an amino acid sequence selected from the group consisting of SEQ ID NO: 1516, 1517, 1519, 1521, 1527, 1528, and 1529; or
an amino acid sequence having no more than one amino acid differences from an amino acid sequence selected from the group consisting of SEQ ID NO: 1516, 1517, 1519, 1521, 1527, 1528, and 1529.
13. The method of claim 1 , wherein said tumor cells are part of a carcinoma.
14. The method of claim 1 , wherein said cancer is tumor cells are part of an ovarian carcinoma.
15. The method of claim 1 , wherein said polypeptide comprises at least two epitopic peptides.
16. The method of claim 15 , wherein said polypeptide comprises at least three epitopic peptides.
17. The method of claim 1 , wherein said composition comprises
an epitopic peptide comprising an amino acid sequence of SEQ ID NO: 1516;
an epitopic peptide comprising an amino acid sequence of SEQ ID NO: 1517;
an epitopic peptide comprising an amino acid sequence of SEQ ID NO: 1519;
an epitopic peptide comprising an amino acid sequence of SEQ ID NO: 1521;
an epitopic peptide comprising an amino acid sequence of SEQ ID NO: 1527;
an epitopic peptide comprising an amino acid sequence of SEQ ID NO: 1528; and
an epitopic peptide comprising an amino acid sequence of SEQ ID NO: 1529.
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US13/030,563 US20110142919A1 (en) | 2000-12-04 | 2011-02-18 | Cytotoxic T-Lymphocyte-Inducing Immunogens for Prevention, Treatment and Diagnosis of Cancer |
Applications Claiming Priority (5)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US25102200P | 2000-12-04 | 2000-12-04 | |
US25682400P | 2000-12-20 | 2000-12-20 | |
US10/006,177 US7083789B2 (en) | 2000-12-04 | 2001-12-04 | Cytotoxic T-lymphocyte-inducing immunogens for prevention, treatment, and diagnosis of cancer |
US11/426,161 US7919467B2 (en) | 2000-12-04 | 2006-06-23 | Cytotoxic T-lymphocyte-inducing immunogens for prevention, treatment, and diagnosis of cancer |
US13/030,563 US20110142919A1 (en) | 2000-12-04 | 2011-02-18 | Cytotoxic T-Lymphocyte-Inducing Immunogens for Prevention, Treatment and Diagnosis of Cancer |
Related Parent Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
US11/426,161 Continuation US7919467B2 (en) | 2000-12-04 | 2006-06-23 | Cytotoxic T-lymphocyte-inducing immunogens for prevention, treatment, and diagnosis of cancer |
Publications (1)
Publication Number | Publication Date |
---|---|
US20110142919A1 true US20110142919A1 (en) | 2011-06-16 |
Family
ID=38834449
Family Applications (2)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
US11/426,161 Expired - Fee Related US7919467B2 (en) | 2000-12-04 | 2006-06-23 | Cytotoxic T-lymphocyte-inducing immunogens for prevention, treatment, and diagnosis of cancer |
US13/030,563 Abandoned US20110142919A1 (en) | 2000-12-04 | 2011-02-18 | Cytotoxic T-Lymphocyte-Inducing Immunogens for Prevention, Treatment and Diagnosis of Cancer |
Family Applications Before (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
US11/426,161 Expired - Fee Related US7919467B2 (en) | 2000-12-04 | 2006-06-23 | Cytotoxic T-lymphocyte-inducing immunogens for prevention, treatment, and diagnosis of cancer |
Country Status (5)
Country | Link |
---|---|
US (2) | US7919467B2 (en) |
EP (1) | EP2043679A4 (en) |
AU (1) | AU2007260824A1 (en) |
CA (1) | CA2659124A1 (en) |
WO (1) | WO2007150077A2 (en) |
Cited By (8)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20190161528A1 (en) * | 2016-04-29 | 2019-05-30 | Immunocore Limited | Claudin-6 peptides |
EP3616712A1 (en) * | 2013-08-05 | 2020-03-04 | Immatics Biotechnologies GmbH | Novel immunotherapy against several tumors, such as lung cancer including nsclc |
US10792333B2 (en) | 2015-11-23 | 2020-10-06 | Immunocore Limited | Peptides derived from actin-like protein 8 (ACTL8) |
CN112345655A (en) * | 2019-08-06 | 2021-02-09 | 大理大学 | Establishing method of wasp venom fingerprint, wasp venom fingerprint and application of wasp venom fingerprint |
US10980893B2 (en) | 2015-11-23 | 2021-04-20 | Immunocore Limited | Peptides derived from transient receptor potential cation channel subfamily M member 1 (TRPM1), complexes comprising such peptides bound to MHC molecules |
US11065314B2 (en) | 2015-12-22 | 2021-07-20 | Immatics Biotechnologies Gmbh | Peptides and combination of peptides for use in immunotherapy against breast cancer and other cancers |
US11136352B2 (en) | 2008-10-01 | 2021-10-05 | Immatics Biotechnologies Gmbh | Immunotherapy against several tumors including neuronal and brain tumors |
US11161880B2 (en) | 2013-08-05 | 2021-11-02 | Immatics Biotechnologies Gmbh | Immunotherapy against several tumors, such as lung cancer, including NSCLC |
Families Citing this family (81)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20090062512A1 (en) * | 2000-10-10 | 2009-03-05 | Hildebrand William H | Comparative ligand mapping from MHC class I positive cells |
US7919467B2 (en) * | 2000-12-04 | 2011-04-05 | Immunotope, Inc. | Cytotoxic T-lymphocyte-inducing immunogens for prevention, treatment, and diagnosis of cancer |
US7811828B2 (en) * | 2004-01-28 | 2010-10-12 | Immatics Biotechnologies Gmbh | Method for identifying and quantifying of tumuor-associated |
BRPI0717651A2 (en) | 2006-10-17 | 2013-12-24 | Oncotherapy Science Inc | PEPTIDE CANCER VACCINES EXPRESSING MPHOSPH1 OR DEPDC1 POLYPEPTIDES |
TWI615403B (en) * | 2007-02-21 | 2018-02-21 | 腫瘤療法 科學股份有限公司 | Peptide vaccines for cancers expressing tumor-associated antigens |
WO2009032256A2 (en) * | 2007-08-30 | 2009-03-12 | Cell Genesys, Inc. | Apc activators in combination with a cytokine-secreting cell and methods of use thereof |
EP2216344B1 (en) * | 2007-11-14 | 2017-06-28 | Chugai Seiyaku Kabushiki Kaisha | Diagnosis and treatment of cancer using anti-gpr49 antibody |
WO2009113674A1 (en) * | 2008-03-14 | 2009-09-17 | 学校法人北里研究所 | Diagnosis of bladder carcinoma |
PL2113253T3 (en) | 2008-04-30 | 2010-09-30 | Immatics Biotechnologies Gmbh | Novel formulations of tumour-associated peptides binding to human leukocyte antigen (HLA) class I or II molecules for vaccines |
WO2010010848A1 (en) * | 2008-07-22 | 2010-01-28 | 第一三共株式会社 | Method for production of antibody in cultured mammalian cell by using molecular chaperone |
DK2322221T3 (en) | 2008-08-05 | 2014-09-01 | Toray Industries | PHARMACEUTICAL COMPOSITION FOR TREATMENT AND PREVENTION OF CANCER |
DK2733492T3 (en) | 2008-08-05 | 2016-04-25 | Toray Industries | Method for detection of cancer |
TW201008574A (en) | 2008-08-19 | 2010-03-01 | Oncotherapy Science Inc | INHBB epitope peptides and vaccines containing the same |
WO2010039223A2 (en) | 2008-09-30 | 2010-04-08 | The Regents Of The University Of California | T-cell immunogens derived from anti-viral proteins and methods of using same |
AU2014271235B2 (en) * | 2008-10-01 | 2017-03-02 | Immatics Biotechnologies Gmbh | Novel immunotherapy against several tumors including neuronal and brain tumors |
AU2016204712B2 (en) * | 2008-10-01 | 2018-03-01 | Immatics Biotechnologies Gmbh | Novel immunotherapy against several tumors including neuronal and brain tumors |
ES2650337T3 (en) | 2009-01-08 | 2018-01-17 | International Institute Of Cancer Immunology, Inc. | Peptides derived from eEF2 for the treatment or prevention of cancers |
FR2942798B1 (en) | 2009-03-05 | 2011-04-08 | Centre Nat Rech Scient | PEPTIDES USEFUL FOR THE TREATMENT OF CHRONIC LYMPHOCYTIC LEUKEMIA |
TW201100090A (en) * | 2009-04-01 | 2011-01-01 | Oncotherapy Science Inc | C6orf167 peptides and vaccines containing the same |
US8075895B2 (en) * | 2009-09-22 | 2011-12-13 | Janssen Pharmaceutica N.V. | Identification of antigenic peptides from multiple myeloma cells |
CN102821788B (en) * | 2010-02-04 | 2016-11-16 | 东丽株式会社 | The treatment of cancer and/or prophylactic compositions |
WO2011096519A1 (en) | 2010-02-04 | 2011-08-11 | 東レ株式会社 | Medicinal composition for treating and/or preventing cancer |
RU2603742C2 (en) | 2010-02-04 | 2016-11-27 | Торэй Индастриз, Инк. | Pharmaceutical composition for treatment and/or prevention of cancer |
KR101843807B1 (en) | 2010-02-04 | 2018-03-30 | 도레이 카부시키가이샤 | Pharmaceutical agent for treatment and/or prevention of cancer |
PT2532366T (en) * | 2010-02-04 | 2016-12-20 | Toray Industries | Pharmaceutical composition for treating and/or preventing cancer |
CA2788545C (en) | 2010-02-04 | 2019-03-26 | Toray Industries, Inc. | Pharmaceutical composition for treating and/or preventing cancer |
AU2015200751B2 (en) * | 2010-03-19 | 2016-11-10 | Immatics Biotechnologies Gmbh | Novel immunotherapy against several tumors including gastrointestinal and gastric cancer |
GB201004551D0 (en) | 2010-03-19 | 2010-05-05 | Immatics Biotechnologies Gmbh | NOvel immunotherapy against several tumors including gastrointestinal and gastric cancer |
TWI538685B (en) * | 2010-04-02 | 2016-06-21 | 腫瘤療法 科學股份有限公司 | Ect2 peptides and vaccines including the same |
CN103429254A (en) * | 2010-10-11 | 2013-12-04 | 南加利福尼亚大学 | Fragment of secreted heat shock protein-90alpha (Hsp90alpha) as vaccines or epitope for monoclonal antibody drugs or target for small molecule drugs against a range of solid human tumors |
WO2012135332A1 (en) * | 2011-03-28 | 2012-10-04 | President And Fellows Of Harvard College | Modulators of plexin b2 activity |
AU2012290954B2 (en) | 2011-08-04 | 2017-08-31 | Toray Industries, Inc. | Pharmaceutical composition for treatment and/or prophylaxis of cancer |
CN103718045B (en) | 2011-08-04 | 2016-08-17 | 东丽株式会社 | The detection method of pancreas cancer |
US9273128B2 (en) | 2011-08-04 | 2016-03-01 | Toray Industries, Inc | Pharmaceutical composition for treatment and/or prophylaxis of cancer |
MX348577B (en) | 2011-08-04 | 2017-06-20 | Toray Industries | Cancer treatment and/or prevention drug composition. |
RU2624049C2 (en) | 2011-08-04 | 2017-06-30 | Торэй Индастриз, Инк. | Pharmaceutical composition for cancer treatment and prevention |
ES2609846T3 (en) | 2011-08-04 | 2017-04-24 | Toray Industries, Inc. | Pharmaceutical composition for the treatment and / or prevention of pancreatic cancer |
CA2844030C (en) | 2011-08-04 | 2019-09-03 | Toray Industries, Inc. | Pharmaceutical composition for treatment and/or prophylaxis of cancer |
WO2013024582A1 (en) | 2011-08-12 | 2013-02-21 | Oncotherapy Science, Inc. | Mphosph1 peptides and vaccines including the same |
EP3228321B1 (en) * | 2011-09-13 | 2019-04-10 | Immunotope, Inc. | Cytotoxic t-lymphocyte-inducing immunogens for prevention, treatment, and diagnosis of cancer |
EP2824114B1 (en) | 2012-02-21 | 2019-05-22 | Toray Industries, Inc. | Pharmaceutical composition for treatment of cancer |
ES2739612T3 (en) | 2012-02-21 | 2020-02-03 | Toray Industries | Pharmaceutical composition for cancer treatment |
RU2631804C2 (en) | 2012-02-21 | 2017-09-26 | Торэй Индастриз, Инк. | Pharmaceutical composition for cancer treatment or prevention |
KR102005308B1 (en) | 2012-02-21 | 2019-07-30 | 도레이 카부시키가이샤 | Pharmaceutical composition for treatment and/or prevention of cancer |
WO2013147169A1 (en) | 2012-03-30 | 2013-10-03 | 東レ株式会社 | Pharmaceutical composition for treatment and/or prevention of liver cancer |
US9428581B2 (en) | 2012-03-30 | 2016-08-30 | Toray Industries, Inc. | Pharmaceutical composition for treatment and/or prevention of gallbladder cancer |
HUE043162T2 (en) | 2012-07-19 | 2019-08-28 | Toray Industries | Method for detecting cancer |
US9753038B2 (en) | 2012-07-19 | 2017-09-05 | Toray Industries, Inc. | Method for detecting cancer via measurement of caprin-1 expression level |
TWI658049B (en) | 2013-03-12 | 2019-05-01 | 腫瘤療法 科學股份有限公司 | Kntc2 peptides and vaccines containing the same |
EP2968536B1 (en) * | 2013-03-13 | 2023-06-28 | The United States of America, as represented by The Secretary, Department of Health and Human Services | Methods for modulating chemotherapeutic cytotoxicity |
CA2918989C (en) | 2013-08-09 | 2021-11-02 | Toray Industries, Inc. | Pharmaceutical composition for treatment and/or prevention of cancer |
CA3174012A1 (en) | 2013-09-13 | 2015-03-19 | Genentech, Inc. | Compositions and methods for detecting and quantifying host cell protein in cell lines and recombinant polypeptide products |
KR102373930B1 (en) | 2013-09-13 | 2022-03-11 | 제넨테크, 인크. | Methods and compositions comprising purified recombinant polypeptides |
GB201322626D0 (en) | 2013-12-19 | 2014-02-05 | Immutep S A | Combined preparations for the treatment of cancer |
WO2015140567A1 (en) * | 2014-03-21 | 2015-09-24 | Immunocore Limited | Tumor associated antigens derived from traip |
WO2015148960A1 (en) | 2014-03-28 | 2015-10-01 | The Board Of Regents Of The University Of Oklahoma | Compositions comprising soluble hla/m. tuberculosis-specific ligand complexes and methods of production and use thereof |
US10000533B2 (en) | 2014-06-20 | 2018-06-19 | Immatics Biotechnologies Gmbh | Immunotherapy against several tumors of the blood, in particular chronic lymphoid leukemia (CLL) |
GB201411037D0 (en) * | 2014-06-20 | 2014-08-06 | Immatics Biotechnologies Gmbh | Novel immunotherapy against several tumors of the blood, in particular chronic lymphoid leukemai (CLL) |
TWI711633B (en) * | 2014-09-24 | 2020-12-01 | 北海道公立大學法人札幌醫科大學 | Tumor antigen peptide |
HUE046641T2 (en) * | 2014-12-23 | 2020-03-30 | Immatics Biotechnologies Gmbh | Novel peptides and combination of peptides for use in immunotherapy against hepatocellular carcinoma (hcc) and other cancers |
GB201500374D0 (en) | 2015-01-09 | 2015-02-25 | Immutep S A | Combined preparations for the treatment of cancer |
US10414813B2 (en) | 2015-02-09 | 2019-09-17 | Université de Montréal | Minor histocompatibility antigens and uses thereof |
PL3388075T3 (en) | 2015-03-27 | 2023-12-11 | Immatics Biotechnologies Gmbh | Novel peptides and combination of peptides for use in immunotherapy against various tumors (seq id 25 - mrax5-003) |
GB201505305D0 (en) | 2015-03-27 | 2015-05-13 | Immatics Biotechnologies Gmbh | Novel Peptides and combination of peptides for use in immunotherapy against various tumors |
US10676508B2 (en) | 2015-08-12 | 2020-06-09 | Oncotherapy Science, Inc. | DEPDC1-derived peptide and vaccine containing same |
WO2017053735A1 (en) * | 2015-09-23 | 2017-03-30 | The United States Of America, As Represented By The Secretary, Department Of Health And Human Services | Human rpn2 derived peptides useful for treating cancer |
GB201517538D0 (en) | 2015-10-05 | 2015-11-18 | Immatics Biotechnologies Gmbh | Novel peptides and combination of peptides for use in immunotherapy against small cell lung cancer and other cancers |
MY198087A (en) | 2015-10-05 | 2023-07-31 | Immatics Biotechnologies Gmbh | Peptides and combination of peptides for use in immunotherapy against small cell lung cancer and other cancers |
JP6857909B2 (en) | 2015-10-08 | 2021-04-14 | オンコセラピー・サイエンス株式会社 | MPHOSPH1-derived peptide and vaccine containing it |
GB201521894D0 (en) | 2015-12-11 | 2016-01-27 | Immatics Biotechnologies Gmbh | Novel peptides and combination of peptides for use in immunotherapy against various cancers |
PE20230343A1 (en) | 2015-12-11 | 2023-03-01 | Immatics Biotechnologies Gmbh | PEPTIDES THAT STIMULATE ANTI-TUMORAL IMMUNE RESPONSES |
US10383896B2 (en) | 2015-12-11 | 2019-08-20 | Immatics Biotechnologies Gmbh | Peptides and combination of peptides for use in immunotherapy against various cancers |
GB201604490D0 (en) * | 2016-03-16 | 2016-04-27 | Immatics Biotechnologies Gmbh | Peptides combination of peptides for use in immunotherapy against cancers |
CN106913863B (en) * | 2017-03-16 | 2020-10-27 | 北京热休生物技术有限公司 | Application of compound of polypeptide of NUP188 protein and heat shock protein gp96 in preparation of medicine for treating and preventing cancer |
IT201800002694A1 (en) * | 2018-02-15 | 2019-08-15 | Sbarro Health Res Organization Inc | MOLECULES THAT INHIBIT PKB / AKT BY COMPROMISING THE SER941 PHOSPHORILATION OF RBL2 / p130 |
JP2021517810A (en) * | 2018-03-12 | 2021-07-29 | ザ・チルドレンズ・ホスピタル・オブ・フィラデルフィアThe Children’S Hospital Of Philadelphia | Methods and Compositions for the Use of Tumor Autoantigens in Adoptive Immunotherapy |
KR102322832B1 (en) * | 2019-04-22 | 2021-11-12 | 한국과학기술연구원 | Human leukocyte antigen A24:02 allele specific binding peptides and uses thereof |
US20220334130A1 (en) * | 2019-08-16 | 2022-10-20 | Research & Business Foundation Sungkyunkwan University | Melanogenesis detection method using fam86a |
KR102372647B1 (en) * | 2019-08-16 | 2022-03-10 | 성균관대학교산학협력단 | Composition for melanin formation detection and Screening method of skin whitening materials |
KR102265431B1 (en) * | 2019-08-20 | 2021-06-15 | 주식회사 케어젠 | Peptides promoting hair growth and uses thereof |
CN113447656B (en) * | 2021-07-01 | 2022-05-13 | 浙江大学 | Kit for detecting anti-filamentous actin cap-forming protein beta-IgG antibody |
Citations (25)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4235871A (en) * | 1978-02-24 | 1980-11-25 | Papahadjopoulos Demetrios P | Method of encapsulating biologically active materials in lipid vesicles |
US4501728A (en) * | 1983-01-06 | 1985-02-26 | Technology Unlimited, Inc. | Masking of liposomes from RES recognition |
US4690915A (en) * | 1985-08-08 | 1987-09-01 | The United States Of America As Represented By The Department Of Health And Human Services | Adoptive immunotherapy as a treatment modality in humans |
US4722848A (en) * | 1982-12-08 | 1988-02-02 | Health Research, Incorporated | Method for immunizing animals with synthetically modified vaccinia virus |
US4837028A (en) * | 1986-12-24 | 1989-06-06 | Liposome Technology, Inc. | Liposomes with enhanced circulation time |
US4844893A (en) * | 1986-10-07 | 1989-07-04 | Scripps Clinic And Research Foundation | EX vivo effector cell activation for target cell killing |
US5019369A (en) * | 1984-10-22 | 1991-05-28 | Vestar, Inc. | Method of targeting tumors in humans |
US5635363A (en) * | 1995-02-28 | 1997-06-03 | The Board Of Trustees Of The Leland Stanford Junior University | Compositions and methods for the detection, quantitation and purification of antigen-specific T cells |
US5645994A (en) * | 1990-07-05 | 1997-07-08 | University Of Utah Research Foundation | Method and compositions for identification of species in a sample using type II topoisomerase sequences |
US5677144A (en) * | 1993-11-16 | 1997-10-14 | Ullrich; Axel | Recombinant DNA encoding CCK 2, a receptor tyrosine kinase |
US5747269A (en) * | 1991-05-17 | 1998-05-05 | Max-Planck-Gesellschaft Zur Forderung Der Wissenschaften E.V. | Determination of peptide motifs on MHC molecules |
US5763219A (en) * | 1995-09-07 | 1998-06-09 | Health Research, Incorporated | Cyclin E variants and use thereof |
US5972643A (en) * | 1994-06-17 | 1999-10-26 | Fred Hutchinson Cancer Research Center | Isolated polynucleotide molecules encoding CTCF, a CCCTC-binding factor |
US6140464A (en) * | 1995-06-07 | 2000-10-31 | Ludwig Institute For Cancer Research | Nonapeptides that bind a HLA-A2.1 molecule |
US6168804B1 (en) * | 1995-06-07 | 2001-01-02 | University Of Alberta | Method for eliciting Th1-specific immune response |
US6548064B1 (en) * | 1997-05-05 | 2003-04-15 | Ludwig Institute For Cancer Research | Isolated peptides consisting of amino acid sequences found in SSX or NY-ESO-1 molecules, which bind to HLA molecules |
US20040236091A1 (en) * | 2001-03-28 | 2004-11-25 | Chicz Roman M. | Translational profiling |
US6867283B2 (en) * | 2001-05-16 | 2005-03-15 | Technion Research & Development Foundation Ltd. | Peptides capable of binding to MHC molecules, cells presenting such peptides, and pharmaceutical compositions comprising such peptides and/or cells |
US7083789B2 (en) * | 2000-12-04 | 2006-08-01 | Immunotope, Inc. | Cytotoxic T-lymphocyte-inducing immunogens for prevention, treatment, and diagnosis of cancer |
US7087712B1 (en) * | 1999-04-16 | 2006-08-08 | Immatics Biotechnologies Gmbh | Peptide for triggering an immune reaction against tumor cells |
US7270819B2 (en) * | 1997-05-05 | 2007-09-18 | Ludwig Institute For Cancer Research | Isolated nucleic acid molecules encoding isolated peptides which correspond to contiguous amino acids of an SSX molecule or NY-ESO-1 and uses thereof |
US20090075304A1 (en) * | 2004-05-27 | 2009-03-19 | Weidanz Jon A | Methods of assaying vaccine potency |
US20090233318A1 (en) * | 2004-12-28 | 2009-09-17 | Weidanz Jon A | Methods of assaying vaccine potency |
US20090304679A1 (en) * | 2004-05-27 | 2009-12-10 | Weidanz Jon A | Antibodies as T cell receptor mimics, methods of production and uses thereof |
US7919467B2 (en) * | 2000-12-04 | 2011-04-05 | Immunotope, Inc. | Cytotoxic T-lymphocyte-inducing immunogens for prevention, treatment, and diagnosis of cancer |
Family Cites Families (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP0615453B1 (en) | 1991-11-29 | 1997-05-14 | Chiron Viagene, Inc. | Anti-cancer immunotherapeutic vector constructs |
JP5490413B2 (en) | 2006-01-05 | 2014-05-14 | ジ・オハイオ・ステイト・ユニバーシティ・リサーチ・ファウンデイション | Abnormal microRNA expression in pancreatic endocrine and acinar tumors |
-
2006
- 2006-06-23 US US11/426,161 patent/US7919467B2/en not_active Expired - Fee Related
-
2007
- 2007-06-25 CA CA002659124A patent/CA2659124A1/en not_active Abandoned
- 2007-06-25 WO PCT/US2007/072059 patent/WO2007150077A2/en active Application Filing
- 2007-06-25 EP EP07799012A patent/EP2043679A4/en not_active Withdrawn
- 2007-06-25 AU AU2007260824A patent/AU2007260824A1/en not_active Abandoned
-
2011
- 2011-02-18 US US13/030,563 patent/US20110142919A1/en not_active Abandoned
Patent Citations (27)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4235871A (en) * | 1978-02-24 | 1980-11-25 | Papahadjopoulos Demetrios P | Method of encapsulating biologically active materials in lipid vesicles |
US4722848A (en) * | 1982-12-08 | 1988-02-02 | Health Research, Incorporated | Method for immunizing animals with synthetically modified vaccinia virus |
US4501728A (en) * | 1983-01-06 | 1985-02-26 | Technology Unlimited, Inc. | Masking of liposomes from RES recognition |
US5019369A (en) * | 1984-10-22 | 1991-05-28 | Vestar, Inc. | Method of targeting tumors in humans |
US4690915A (en) * | 1985-08-08 | 1987-09-01 | The United States Of America As Represented By The Department Of Health And Human Services | Adoptive immunotherapy as a treatment modality in humans |
US4844893A (en) * | 1986-10-07 | 1989-07-04 | Scripps Clinic And Research Foundation | EX vivo effector cell activation for target cell killing |
US4837028A (en) * | 1986-12-24 | 1989-06-06 | Liposome Technology, Inc. | Liposomes with enhanced circulation time |
US5645994A (en) * | 1990-07-05 | 1997-07-08 | University Of Utah Research Foundation | Method and compositions for identification of species in a sample using type II topoisomerase sequences |
US5747269A (en) * | 1991-05-17 | 1998-05-05 | Max-Planck-Gesellschaft Zur Forderung Der Wissenschaften E.V. | Determination of peptide motifs on MHC molecules |
US5677144A (en) * | 1993-11-16 | 1997-10-14 | Ullrich; Axel | Recombinant DNA encoding CCK 2, a receptor tyrosine kinase |
US5972643A (en) * | 1994-06-17 | 1999-10-26 | Fred Hutchinson Cancer Research Center | Isolated polynucleotide molecules encoding CTCF, a CCCTC-binding factor |
US5635363A (en) * | 1995-02-28 | 1997-06-03 | The Board Of Trustees Of The Leland Stanford Junior University | Compositions and methods for the detection, quantitation and purification of antigen-specific T cells |
US6140464A (en) * | 1995-06-07 | 2000-10-31 | Ludwig Institute For Cancer Research | Nonapeptides that bind a HLA-A2.1 molecule |
US6168804B1 (en) * | 1995-06-07 | 2001-01-02 | University Of Alberta | Method for eliciting Th1-specific immune response |
US5763219A (en) * | 1995-09-07 | 1998-06-09 | Health Research, Incorporated | Cyclin E variants and use thereof |
US6548064B1 (en) * | 1997-05-05 | 2003-04-15 | Ludwig Institute For Cancer Research | Isolated peptides consisting of amino acid sequences found in SSX or NY-ESO-1 molecules, which bind to HLA molecules |
US7270819B2 (en) * | 1997-05-05 | 2007-09-18 | Ludwig Institute For Cancer Research | Isolated nucleic acid molecules encoding isolated peptides which correspond to contiguous amino acids of an SSX molecule or NY-ESO-1 and uses thereof |
US7087712B1 (en) * | 1999-04-16 | 2006-08-08 | Immatics Biotechnologies Gmbh | Peptide for triggering an immune reaction against tumor cells |
US7083789B2 (en) * | 2000-12-04 | 2006-08-01 | Immunotope, Inc. | Cytotoxic T-lymphocyte-inducing immunogens for prevention, treatment, and diagnosis of cancer |
US7919467B2 (en) * | 2000-12-04 | 2011-04-05 | Immunotope, Inc. | Cytotoxic T-lymphocyte-inducing immunogens for prevention, treatment, and diagnosis of cancer |
US20040236091A1 (en) * | 2001-03-28 | 2004-11-25 | Chicz Roman M. | Translational profiling |
US6867283B2 (en) * | 2001-05-16 | 2005-03-15 | Technion Research & Development Foundation Ltd. | Peptides capable of binding to MHC molecules, cells presenting such peptides, and pharmaceutical compositions comprising such peptides and/or cells |
US20090075304A1 (en) * | 2004-05-27 | 2009-03-19 | Weidanz Jon A | Methods of assaying vaccine potency |
US20090304679A1 (en) * | 2004-05-27 | 2009-12-10 | Weidanz Jon A | Antibodies as T cell receptor mimics, methods of production and uses thereof |
US20140065708A1 (en) * | 2004-05-27 | 2014-03-06 | Receptor Logic, LLC | Antibodies as t cell receptor mimics, methods of production and uses thereof |
US20140141455A1 (en) * | 2004-05-27 | 2014-05-22 | Receptor Logic, Inc. | Methods of assaying vaccine potency |
US20090233318A1 (en) * | 2004-12-28 | 2009-09-17 | Weidanz Jon A | Methods of assaying vaccine potency |
Non-Patent Citations (1)
Title |
---|
Ibragimova and Eade (Biophysical Journal, Oct 1999, Vol. 77, pp. 2191-2198) * |
Cited By (15)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US11136352B2 (en) | 2008-10-01 | 2021-10-05 | Immatics Biotechnologies Gmbh | Immunotherapy against several tumors including neuronal and brain tumors |
US11208434B2 (en) | 2008-10-01 | 2021-12-28 | Immatics Biotechnologies Gmbh | Immunotherapy against several tumors including neuronal and brain tumors |
TWI777194B (en) * | 2013-08-05 | 2022-09-11 | 德商伊瑪提克斯生物科技有限公司 | Novel peptides, cells, and their use against several tumors, methods for production thereof and pharmaceutical composition comprising the same |
US11161880B2 (en) | 2013-08-05 | 2021-11-02 | Immatics Biotechnologies Gmbh | Immunotherapy against several tumors, such as lung cancer, including NSCLC |
EP3616712A1 (en) * | 2013-08-05 | 2020-03-04 | Immatics Biotechnologies GmbH | Novel immunotherapy against several tumors, such as lung cancer including nsclc |
US11814446B2 (en) | 2013-08-05 | 2023-11-14 | Immatics Biotechnologies Gmbh | Immunotherapy against several tumors including lung cancer |
US11859017B2 (en) | 2013-08-05 | 2024-01-02 | Immatics Biotechnologies Gmbh | Immunotherapy against several tumors including lung cancer |
US11866517B2 (en) | 2013-08-05 | 2024-01-09 | Immatics Biotechnologies Gmbh | Immunotherapy against several tumors including lung cancer |
US11939401B2 (en) | 2013-08-05 | 2024-03-26 | Immatics Biotechnologies Gmbh | Immunotherapy against several tumors including lung cancer |
US11939400B2 (en) | 2013-08-05 | 2024-03-26 | Immatics Biotechnologies Gmbh | Immunotherapy against several tumors including lung cancer |
US10980893B2 (en) | 2015-11-23 | 2021-04-20 | Immunocore Limited | Peptides derived from transient receptor potential cation channel subfamily M member 1 (TRPM1), complexes comprising such peptides bound to MHC molecules |
US10792333B2 (en) | 2015-11-23 | 2020-10-06 | Immunocore Limited | Peptides derived from actin-like protein 8 (ACTL8) |
US11065314B2 (en) | 2015-12-22 | 2021-07-20 | Immatics Biotechnologies Gmbh | Peptides and combination of peptides for use in immunotherapy against breast cancer and other cancers |
US20190161528A1 (en) * | 2016-04-29 | 2019-05-30 | Immunocore Limited | Claudin-6 peptides |
CN112345655A (en) * | 2019-08-06 | 2021-02-09 | 大理大学 | Establishing method of wasp venom fingerprint, wasp venom fingerprint and application of wasp venom fingerprint |
Also Published As
Publication number | Publication date |
---|---|
CA2659124A1 (en) | 2007-12-27 |
US7919467B2 (en) | 2011-04-05 |
WO2007150077A8 (en) | 2008-08-28 |
AU2007260824A1 (en) | 2007-12-27 |
EP2043679A2 (en) | 2009-04-08 |
EP2043679A4 (en) | 2010-04-14 |
WO2007150077A2 (en) | 2007-12-27 |
US20080207497A1 (en) | 2008-08-28 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
US7919467B2 (en) | Cytotoxic T-lymphocyte-inducing immunogens for prevention, treatment, and diagnosis of cancer | |
US9907842B2 (en) | Cytotoxic T lymphocyte inducing immunogens for prevention treatment and diagnosis of cancer | |
US20080107668A1 (en) | Cytotoxic t-lymphocyte-inducing immunogens for prevention, treatment, and diagnosis of cancer | |
CA2188432C (en) | Melanoma antigens | |
KR100653590B1 (en) | Tumor antigen peptides originating in cyclophilin b | |
Kawakami et al. | Cloning of the gene coding for a shared human melanoma antigen recognized by autologous T cells infiltrating into tumor. | |
US20070248628A1 (en) | Immunogens in cancer stem cells | |
US5844075A (en) | Melanoma antigens and their use in diagnostic and therapeutic methods | |
EP1691824B1 (en) | Proteins belonging to the bcl-2 family and fragments thereof, and their use in cancer patients | |
RU2435782C2 (en) | Hla a*3303-restricted peptide wt1 and pharmaceutical composition containing said peptide | |
PT2014673E (en) | Tumour-associated peptides which bind to mhc molecules | |
WO2009036246A2 (en) | Immunogens that induce cytotoxic t-lymphocytes and their use in prevention, treatment, and diagnosis of cancer | |
EP1430076A2 (en) | Polypeptides derived from inducible hsp70 and pharmaceutical compositions containing the same | |
US8252545B2 (en) | Peptides of a melanoma antigen and their use in diagnostic, prophylactic, and therapeutic methods | |
JP4365405B2 (en) | Tumor associated peptides that bind to MHC molecules | |
KR20010080661A (en) | Novel tumor antigen protein art-1 and tumor antigen peptide thereof | |
US7476535B2 (en) | TRP2 isoform TRP2-6b containing HLA-A2 restricted epitopes | |
AU2002338804A1 (en) | Polypeptides derived from inducible Hsp70 and pharmaceutical compositions containing the same |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
STCB | Information on status: application discontinuation |
Free format text: ABANDONED -- FAILURE TO RESPOND TO AN OFFICE ACTION |