DE19602985A1 - Tumour vaccine for treatment of, e.g., carcinoma melanoma or leukaemia - Google Patents
Tumour vaccine for treatment of, e.g., carcinoma melanoma or leukaemiaInfo
- Publication number
- DE19602985A1 DE19602985A1 DE19602985A DE19602985A DE19602985A1 DE 19602985 A1 DE19602985 A1 DE 19602985A1 DE 19602985 A DE19602985 A DE 19602985A DE 19602985 A DE19602985 A DE 19602985A DE 19602985 A1 DE19602985 A1 DE 19602985A1
- Authority
- DE
- Germany
- Prior art keywords
- tumor cells
- tumor
- cell vaccine
- gene
- tumor cell
- 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.)
- Withdrawn
Links
- 206010028980 Neoplasm Diseases 0.000 title claims abstract description 14
- 238000011282 treatment Methods 0.000 title claims description 6
- 208000032839 leukemia Diseases 0.000 title claims description 4
- 201000009030 Carcinoma Diseases 0.000 title claims description 3
- 201000001441 melanoma Diseases 0.000 title claims description 3
- 229960005486 vaccine Drugs 0.000 title abstract description 5
- 210000004881 tumor cell Anatomy 0.000 claims abstract description 25
- 108090000623 proteins and genes Proteins 0.000 claims abstract description 13
- 102000002812 Heat-Shock Proteins Human genes 0.000 claims abstract description 12
- 108010004889 Heat-Shock Proteins Proteins 0.000 claims abstract description 12
- 238000009169 immunotherapy Methods 0.000 claims abstract description 3
- 229940030325 tumor cell vaccine Drugs 0.000 claims description 17
- 241000606153 Chlamydia trachomatis Species 0.000 claims description 4
- 229940038705 chlamydia trachomatis Drugs 0.000 claims description 4
- 241000588724 Escherichia coli Species 0.000 claims description 3
- 206010025323 Lymphomas Diseases 0.000 claims description 2
- 206010039491 Sarcoma Diseases 0.000 claims description 2
- 230000000735 allogeneic effect Effects 0.000 claims description 2
- 208000035250 cutaneous malignant susceptibility to 1 melanoma Diseases 0.000 claims description 2
- 230000000813 microbial effect Effects 0.000 claims description 2
- 101710163595 Chaperone protein DnaK Proteins 0.000 claims 3
- 101710178376 Heat shock 70 kDa protein Proteins 0.000 claims 3
- 101710152018 Heat shock cognate 70 kDa protein Proteins 0.000 claims 3
- 102100021410 Heat shock 70 kDa protein 14 Human genes 0.000 claims 1
- 101001041756 Homo sapiens Heat shock 70 kDa protein 14 Proteins 0.000 claims 1
- 101000944608 Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv) Chaperonin GroEL 2 Proteins 0.000 claims 1
- 201000011510 cancer Diseases 0.000 description 4
- 230000003053 immunization Effects 0.000 description 4
- 238000002649 immunization Methods 0.000 description 4
- 230000005847 immunogenicity Effects 0.000 description 4
- 101000839464 Leishmania braziliensis Heat shock 70 kDa protein Proteins 0.000 description 3
- 230000007123 defense Effects 0.000 description 3
- 206010027476 Metastases Diseases 0.000 description 2
- 208000003788 Neoplasm Micrometastasis Diseases 0.000 description 2
- 239000004480 active ingredient Substances 0.000 description 2
- 239000000427 antigen Substances 0.000 description 2
- 102000036639 antigens Human genes 0.000 description 2
- 108091007433 antigens Proteins 0.000 description 2
- 210000004027 cell Anatomy 0.000 description 2
- 238000010353 genetic engineering Methods 0.000 description 2
- 210000002865 immune cell Anatomy 0.000 description 2
- 230000001900 immune effect Effects 0.000 description 2
- 230000028993 immune response Effects 0.000 description 2
- 241000894006 Bacteria Species 0.000 description 1
- 206010009944 Colon cancer Diseases 0.000 description 1
- 102000007644 Colony-Stimulating Factors Human genes 0.000 description 1
- 108010071942 Colony-Stimulating Factors Proteins 0.000 description 1
- 102000004127 Cytokines Human genes 0.000 description 1
- 108090000695 Cytokines Proteins 0.000 description 1
- 101000738180 Euglena gracilis Chaperonin CPN60, mitochondrial Proteins 0.000 description 1
- 102000014150 Interferons Human genes 0.000 description 1
- 108010050904 Interferons Proteins 0.000 description 1
- 241000700605 Viruses Species 0.000 description 1
- 230000000890 antigenic effect Effects 0.000 description 1
- 238000004113 cell culture Methods 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 238000002512 chemotherapy Methods 0.000 description 1
- 229940047120 colony stimulating factors Drugs 0.000 description 1
- 230000000139 costimulatory effect Effects 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 238000006911 enzymatic reaction Methods 0.000 description 1
- 210000000987 immune system Anatomy 0.000 description 1
- 230000002163 immunogen Effects 0.000 description 1
- 229940047124 interferons Drugs 0.000 description 1
- 238000010297 mechanical methods and process Methods 0.000 description 1
- 230000002980 postoperative effect Effects 0.000 description 1
- 230000005855 radiation Effects 0.000 description 1
- 230000002285 radioactive effect Effects 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 238000001356 surgical procedure Methods 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 230000001960 triggered effect Effects 0.000 description 1
- 238000002255 vaccination Methods 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K48/00—Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
-
- 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
- A61K39/001176—Heat shock proteins
-
- 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
- A61K2039/5152—Tumor 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
- A61K2039/515—Animal cells
- A61K2039/5156—Animal cells expressing foreign proteins
Abstract
Description
Die Erfindung betrifft die Herstellung eines gentechnisch modifizierten Tumorzellimpfstoffes für die Immuntherapie von malignen Tumoren. Anwendungsgebiete der Erfindung sind die Medizin und die pharmazeutische Industrie.The invention relates to the production of a genetically engineered modified tumor cell vaccine for the immunotherapy of malignant tumors. Areas of application of the invention are Medicine and the pharmaceutical industry.
Die grundlegende Behandlung von Patienten mit einem soliden malignen Tumor ist die chirurgische oder strahlen therapeutische Entfernung des Primärtumors. Allerdings besteht auch nach kompletter Entfernung des Primärtumors das Risiko, daß Mikrometastasen, die bereits zum Zeitpunkt der Operation existierten, in der postoperativen Phase zu lebensbedrohlichen Metastasen auswachsen. Um die Metastasen zu bekämpfen, wird neben einer chemotherapeutischen Behandlung der Patienten auch versucht, die immunologische Abwehrbereitschaft des Patienten gegen die Tumorzellen wirksam zu stärken. Dies kann durch eine aktive spezifische oder passive Immunisierung geschehen. Die aktive spezifische Immunisierung verfolgt das Ziel, das Immunsystem des Patienten durch Impfung mit devitalisierten Tumorzellen oder definierten tumorassoziierten Antigenen derart zu aktivieren, daß tumorspezifische Abwehrzellen oder Antikörper gebildet werden, die die Mikrometastasen eliminieren oder zumindest deren Wachstum merklich hemmen. Diese Therapieform kann auch zur Behandlung von Patienten mit Leukämie in der Remissionsphase eingesetzt werden. Eine Variante der aktiven spezifischen Immunisierung besteht darin, daß man Immunzellen des Patienten extrakorporal, in der Zellkultur mit Hilfe devitalisierter Tumorzellen oder definierter löslicher tumorassoziierter Antigene tumorspezifisch aktiviert und vermehrt und die derart aktivierten Immunzellen in den Patienten retransfundiert.The basic treatment for patients with a solid malignant tumor is surgical or radiate therapeutic removal of the primary tumor. Indeed even after complete removal of the primary tumor Risk of micrometastases already occurring at the time of Surgery existed in the postoperative period too outgrow life-threatening metastases. To the metastases Combat is next to a chemotherapy Treatment of patients also tried the immunological Defense of the patient against the tumor cells to strengthen effectively. This can be done through an active specific or passive immunization happen. The active specific Immunization aims to improve the immune system of the Patients by vaccination with devitalized tumor cells or to activate defined tumor-associated antigens in such a way that tumor-specific defense cells or antibodies are formed that eliminate or at least eliminate the micrometastases noticeably inhibit their growth. This form of therapy can also for the treatment of patients with leukemia in the Remission phase can be used. A variant of the active specific immunization is that you have immune cells of the patient extracorporeally, in the cell culture with the help devitalized tumor cells or defined soluble tumor-associated antigens are tumor-specifically activated and increased and the activated immune cells in the Retransfused patient.
Nachteilig für die aktive spezifische Immunisierung ist, daß die Tumorzellen des Menschen in den meisten Fällen eine zu geringe Immunogenität besitzen, um per se eine wirksame immunologische Abwehrreaktion auslösen zu können. Daher ist man darauf angewiesen, die Immunogenität der als Impfstoff vorgesehenen Tumorzellen künstlich zu erhöhen. Dieses kann dadurch geschehen, daß man die Tumorzellen chemisch oder enzymatisch verändert (Prager et. al., Ann NY Acad Sci 276, 61-64 (1976)). Auch ein Hinzufügen apathogener Viren (Cassel et. al, Cancer 52, 856-860 (1983)) oder abgeschwächter Tuberkelbakterien/BCG/(Hanna et. al., Cancer Immunol Immunother 7, 165-173 (1979)) kann die Immunogenität eines Tumorzellimpfstoffes steigern. Mit Hilfe der Gentechnik hat man Gene unterschiedlicher Wirkstoffe in Tumorzellen übertragen, ebenfalls mit der Zielstellung, die von dem Tumorzellimpfstoff ausgelöste Immunantwort zu verstärken (Pardoll, Curr Opin Immunol 4, 619-623 (1992)). Der Gentransfer in Tumorzellen betrifft u. a. Zytokine, Interferone, Kolonie-stimulierende Faktoren, Histokompati bilitätsantigene oder costimulatorisch wirkende Faktoren der Immunantwort, sämtlich Wirkstoffe humaner Herkunft. Trotz mancher Erfolge ist es aber bisher nicht gelungen, einen klinisch überzeugenden Tumorzellimpfstoff zu entwickeln. A disadvantage of the active specific immunization is that human tumor cells in most cases one too have low immunogenicity to be effective per se to be able to trigger an immunological defense reaction. thats why one relied on the immunogenicity of the vaccine intended to artificially increase tumor cells. This can happen by chemically or enzymatically changed (Prager et. al., Ann NY Acad Sci 276, 61-64 (1976)). Also adding apathogenic viruses (Cassel et al., Cancer 52, 856-860 (1983)) or weakened tubercle bacteria / BCG / (Hanna et. al., Cancer Immunol Immunother 7, 165-173 (1979)) can Increase immunogenicity of a tumor cell vaccine. With help Genetic engineering has genes of different active ingredients in Tumor cells transferred, also with the aim of immune response triggered by the tumor cell vaccine intensify (Pardoll, Curr Opin Immunol 4, 619-623 (1992)). The gene transfer in tumor cells affects u. a. Cytokines, Interferons, colony stimulating factors, histocompati factors of balance-antigenic or costimulatory effects Immune response, all active ingredients of human origin. Despite However, some successes have so far not been successful to develop clinically convincing tumor cell vaccine.
Das Ziel der vorliegenden Erfindung ist es, die Immunogenität der als Impfstoff verwendeten Tumorzellen durch gentechnische Modifizierung der Tumorzellen wirksam zu verstärken.The aim of the present invention is to improve immunogenicity of the tumor cells used as vaccine by genetic engineering Modify tumor cells effectively.
Dieses Ziel wird erfindungsgemäß durch einen Tumorzellimpfstoff erreicht, der aus Tumorzellen besteht, die zusätzlich das Gen eines exogenen Hitzeschockproteins enthalten. Die wichtigste Ausführungsform der Erfindung besteht darin, das Gen eines mikrobiellen Hitzeschockproteins zu verwenden. Bevorzugt ist der Einsatz von Hitzeschockproteinen aus Mycobakterien, Escherichia coli und aus Chlamydia trachomatis. Besonders bevorzugt sind die Hitzeschockproteine HSP 65 und HSP 70 aus Mycobakterien, HSP 70 aus Escherichia coli (DnaK) sowie HSP 60 und HSP 70 aus Chlamydia trachomatis.According to the invention, this goal is achieved by a Tumor cell vaccine reached, which consists of tumor cells that additionally the gene of an exogenous heat shock protein contain. The most important embodiment of the invention is the gene of a microbial heat shock protein to use. The use of is preferred Heat shock proteins from Mycobacteria, Escherichia coli and from Chlamydia trachomatis. Those are particularly preferred Heat shock proteins HSP 65 and HSP 70 from mycobacteria, HSP 70 from Escherichia coli (DnaK) as well as HSP 60 and HSP 70 Chlamydia trachomatis.
Zur Herstellung des Tumorzellimpfstoffes eignen sich autologe Tumorzellen, die mit Hilfe mechanischer oder enzymatischer Methoden aus chirurgisch entferntem Tumorgewebe isoliert werden. Tumorzellinien, die von allogenen Tumoren gleicher Histologie stammen, können ebenfalls verwendet werden, ein Beispiel dafür sind Zellen einer Colonkarzinomlinie. Der Tumorzellimpfstoff wird postoperativ verabfolgt, vor der Applikation werden die Tumorzellen durch radioaktive Bestrahlung devitalisiert.Autologous are suitable for the production of the tumor cell vaccine Tumor cells using mechanical or enzymatic Methods isolated from surgically removed tumor tissue will. Tumor cell lines that are the same from allogeneic tumors Histology can also be used Examples of this are cells from a colon carcinoma line. Of the Tumor cell vaccine is administered postoperatively before The tumor cells are applied by radioactive Radiation devitalized.
Mit der Herstellung des erfindungsgemäßen Tumorzell impfstoffes wird eine neuartige Strategie verfolgt. Durch Einschleusen des Gens eines exogenen Hitzeschockproteins und dessen Expression werden die Tumorzellen nachhaltig verfremdet und damit stärker immunogen. Nach dieser Strategie können Tumorzellimpfstoffe für die Behandlung von Patienten mit Karzinom, Sarkom, malignem Melanom, Leukämie oder malignem Lymphom hergestellt werden.With the production of the tumor cell according to the invention vaccine is pursuing a new strategy. By Injecting the gene of an exogenous heat shock protein and the tumor cells' expression becomes sustainable alienated and therefore more immunogenic. According to this strategy can use tumor cell vaccines for the treatment of patients with carcinoma, sarcoma, malignant melanoma, leukemia or malignant lymphoma.
Claims (9)
Priority Applications (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE19602985A DE19602985A1 (en) | 1996-01-27 | 1996-01-27 | Tumour vaccine for treatment of, e.g., carcinoma melanoma or leukaemia |
| PCT/DE1997/000172 WO1997026910A2 (en) | 1996-01-27 | 1997-01-27 | Tumour vaccine for immunotherapy of malignant tumours |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE19602985A DE19602985A1 (en) | 1996-01-27 | 1996-01-27 | Tumour vaccine for treatment of, e.g., carcinoma melanoma or leukaemia |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| DE19602985A1 true DE19602985A1 (en) | 1997-07-31 |
Family
ID=7783887
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DE19602985A Withdrawn DE19602985A1 (en) | 1996-01-27 | 1996-01-27 | Tumour vaccine for treatment of, e.g., carcinoma melanoma or leukaemia |
Country Status (1)
| Country | Link |
|---|---|
| DE (1) | DE19602985A1 (en) |
Cited By (20)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5830464A (en) * | 1997-02-07 | 1998-11-03 | Fordham University | Compositions and methods for the treatment and growth inhibition of cancer using heat shock/stress protein-peptide complexes in combination with adoptive immunotherapy |
| US5837251A (en) * | 1995-09-13 | 1998-11-17 | Fordham University | Compositions and methods using complexes of heat shock proteins and antigenic molecules for the treatment and prevention of neoplastic diseases |
| US5935576A (en) * | 1995-09-13 | 1999-08-10 | Fordham University | Compositions and methods for the treatment and prevention of neoplastic diseases using heat shock proteins complexed with exogenous antigens |
| US5948646A (en) * | 1997-12-11 | 1999-09-07 | Fordham University | Methods for preparation of vaccines against cancer comprising heat shock protein-peptide complexes |
| US5961979A (en) * | 1994-03-16 | 1999-10-05 | Mount Sinai School Of Medicine Of The City University Of New York | Stress protein-peptide complexes as prophylactic and therapeutic vaccines against intracellular pathogens |
| US5997873A (en) * | 1994-01-13 | 1999-12-07 | Mount Sinai School Of Medicine Of The City University Of New York | Method of preparation of heat shock protein 70-peptide complexes |
| US6017540A (en) * | 1997-02-07 | 2000-01-25 | Fordham University | Prevention and treatment of primary and metastatic neoplastic diseases and infectious diseases with heat shock/stress protein-peptide complexes |
| US6130087A (en) * | 1996-10-07 | 2000-10-10 | Fordham University | Methods for generating cytotoxic T cells in vitro |
| US6156302A (en) * | 1995-09-13 | 2000-12-05 | Fordham University | Adoptive immunotherapy using macrophages sensitized with heat shock protein-epitope complexes |
| US6451316B1 (en) | 1998-10-05 | 2002-09-17 | University Of Conneticut Health Center | Methods for generating antigen-reactive T cells in vitro |
| US7449557B2 (en) | 2000-06-02 | 2008-11-11 | University Of Connecticut Health Center | Complexes of alpha (2) macroglobulin and antigenic molecules for immunotherapy |
| US7666581B2 (en) | 2001-08-20 | 2010-02-23 | University Of Connecticut Health Center | Methods for preparing compositions comprising heat shock proteins useful for the treatment of cancer and infectious disease |
| US8475785B2 (en) | 2008-03-03 | 2013-07-02 | The University Of Miami | Allogeneic cancer cell-based immunotherapy |
| US8541002B2 (en) | 2003-09-12 | 2013-09-24 | Agenus Inc. | Vaccine for treatment and prevention of herpes simplex virus infection |
| US8685384B2 (en) | 1998-02-20 | 2014-04-01 | University Of Miami | Recombinant cancer cell secreting modified heat shock protein-antigenic peptide complex |
| US10046047B2 (en) | 2015-02-06 | 2018-08-14 | Heat Biologics, Inc. | Vector co-expressing vaccine and costimulatory molecules |
| US10568948B2 (en) | 2015-05-13 | 2020-02-25 | Agenus Inc. | Vaccines for treatment and prevention of cancer |
| US11065317B2 (en) | 2018-04-26 | 2021-07-20 | Agenus Inc. | Heat shock protein-binding peptide compositions and methods of use thereof |
| US11548930B2 (en) | 2017-04-04 | 2023-01-10 | Heat Biologics, Inc. | Intratumoral vaccination |
| US11666649B2 (en) | 2016-10-11 | 2023-06-06 | University Of Miami | Vectors and vaccine cells for immunity against Zika virus |
-
1996
- 1996-01-27 DE DE19602985A patent/DE19602985A1/en not_active Withdrawn
Cited By (48)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5997873A (en) * | 1994-01-13 | 1999-12-07 | Mount Sinai School Of Medicine Of The City University Of New York | Method of preparation of heat shock protein 70-peptide complexes |
| US6168793B1 (en) | 1994-01-13 | 2001-01-02 | Mount Sinai School Of Medicine Of New York University | Heat shock protein 70 preparations in vaccination against cancer and infectious disease |
| US6455503B1 (en) | 1994-03-16 | 2002-09-24 | Mount Sinai School Of Medicine Of New York University | Stress protein-peptide complexes as prophylactic and therapeutic vaccines against intracellular pathogens |
| US6048530A (en) * | 1994-03-16 | 2000-04-11 | Mount Sinai School Of Medicine Of New York University | Stress protein-peptide complexes as prophylactic and therapeutic vaccines against intracellular pathogens |
| US5961979A (en) * | 1994-03-16 | 1999-10-05 | Mount Sinai School Of Medicine Of The City University Of New York | Stress protein-peptide complexes as prophylactic and therapeutic vaccines against intracellular pathogens |
| US6162436A (en) * | 1995-09-13 | 2000-12-19 | Fordham University | Compositions and methods using complexes of heat shock protein 90 and antigenic molecules for the treatment and prevention of neoplastic diseases |
| US5837251A (en) * | 1995-09-13 | 1998-11-17 | Fordham University | Compositions and methods using complexes of heat shock proteins and antigenic molecules for the treatment and prevention of neoplastic diseases |
| US6030618A (en) * | 1995-09-13 | 2000-02-29 | Fordham University | Therapeutic and prophylactic methods using heat shock proteins |
| US7601359B1 (en) | 1995-09-13 | 2009-10-13 | Fordham University | Compositions and methods for the prevention and treatment of primary and metastatic neoplastic diseases and infectious diseases with heat shock/stress proteins |
| US6410028B1 (en) | 1995-09-13 | 2002-06-25 | Fordham University | Therapeutic and prophylactic methods using heat shock proteins |
| US6136315A (en) * | 1995-09-13 | 2000-10-24 | Fordham University | Compositions and methods using complexes of heat shock protein 70 and antigenic molecules for the treatment and prevention of neoplastic diseases |
| US6139841A (en) * | 1995-09-13 | 2000-10-31 | Fordham University | Compositions and methods using complexes of heat shock protein 70 and antigenic molecules for the treatment and prevention of infectious diseases |
| US6143299A (en) * | 1995-09-13 | 2000-11-07 | Fordham University | Compositions and methods using complexes of heat shock protein gp96 and antigenic molecules for the treatment and prevention of infectious diseases |
| US6156302A (en) * | 1995-09-13 | 2000-12-05 | Fordham University | Adoptive immunotherapy using macrophages sensitized with heat shock protein-epitope complexes |
| US5935576A (en) * | 1995-09-13 | 1999-08-10 | Fordham University | Compositions and methods for the treatment and prevention of neoplastic diseases using heat shock proteins complexed with exogenous antigens |
| US6461615B1 (en) | 1995-09-13 | 2002-10-08 | Fordham University | Therapeutic and prophylactic methods using heat shock proteins |
| US6187312B1 (en) | 1995-09-13 | 2001-02-13 | Fordham University | Compositions and methods using complexes of heat shock protein 90 and antigenic molecules for the treatment and prevention of infectious diseases |
| US6447781B1 (en) | 1995-09-13 | 2002-09-10 | Fordham University | Therapeutic and prophylactic methods using heat shock proteins |
| US6130087A (en) * | 1996-10-07 | 2000-10-10 | Fordham University | Methods for generating cytotoxic T cells in vitro |
| US6383493B1 (en) | 1997-02-07 | 2002-05-07 | Fordham University | Methods and compositions for eliciting an immune response with hsp70-peptide complexes |
| US6387374B1 (en) | 1997-02-07 | 2002-05-14 | Fordham University | Treatment of primary and metastatic neoplastic diseases with hsp90-peptide complexes |
| US6399070B1 (en) | 1997-02-07 | 2002-06-04 | Fordham University | Methods and compositions for eliciting an immune response with hsp90-peptide complexes |
| US6403095B1 (en) | 1997-02-07 | 2002-06-11 | Fordham University | Treatment of primary and metastatic neoplastic diseases with HSP70-peptide complexes |
| US6383494B1 (en) | 1997-02-07 | 2002-05-07 | Fordham University | Methods and composition for eliciting an immune response with gp96-peptide complexes |
| US5830464A (en) * | 1997-02-07 | 1998-11-03 | Fordham University | Compositions and methods for the treatment and growth inhibition of cancer using heat shock/stress protein-peptide complexes in combination with adoptive immunotherapy |
| US6455048B1 (en) | 1997-02-07 | 2002-09-24 | Fordham University | Prevention of primary and metastatic neoplastic diseases with hsp70-peptide complexes |
| US6017540A (en) * | 1997-02-07 | 2000-01-25 | Fordham University | Prevention and treatment of primary and metastatic neoplastic diseases and infectious diseases with heat shock/stress protein-peptide complexes |
| US6436404B1 (en) | 1997-02-07 | 2002-08-20 | Fordham University | Prevention of primary and metastatic neoplastic diseases with GP96-peptide complexes |
| US6322790B1 (en) | 1997-02-07 | 2001-11-27 | Fordham University | Compositions and methods for eliciting an immune response using heat shock/stress protein-peptide complexes in combination with adoptive immunotherapy |
| US6447780B1 (en) | 1997-02-07 | 2002-09-10 | Fordham University | Prevention of primary and metastatic neoplastic diseases with hsp90-peptide complexes |
| US6410026B1 (en) | 1997-12-11 | 2002-06-25 | Fordham University | Methods for preparation of vaccines against cancer |
| US5948646A (en) * | 1997-12-11 | 1999-09-07 | Fordham University | Methods for preparation of vaccines against cancer comprising heat shock protein-peptide complexes |
| US6410027B1 (en) | 1997-12-11 | 2002-06-25 | Fordham University | Methods for preparation of vaccines against cancer |
| US6406700B1 (en) | 1997-12-11 | 2002-06-18 | Fordham University | Methods for preparation of vaccines against cancer |
| US8685384B2 (en) | 1998-02-20 | 2014-04-01 | University Of Miami | Recombinant cancer cell secreting modified heat shock protein-antigenic peptide complex |
| US6451316B1 (en) | 1998-10-05 | 2002-09-17 | University Of Conneticut Health Center | Methods for generating antigen-reactive T cells in vitro |
| US7449557B2 (en) | 2000-06-02 | 2008-11-11 | University Of Connecticut Health Center | Complexes of alpha (2) macroglobulin and antigenic molecules for immunotherapy |
| US7666581B2 (en) | 2001-08-20 | 2010-02-23 | University Of Connecticut Health Center | Methods for preparing compositions comprising heat shock proteins useful for the treatment of cancer and infectious disease |
| US8541002B2 (en) | 2003-09-12 | 2013-09-24 | Agenus Inc. | Vaccine for treatment and prevention of herpes simplex virus infection |
| US8475785B2 (en) | 2008-03-03 | 2013-07-02 | The University Of Miami | Allogeneic cancer cell-based immunotherapy |
| US9238064B2 (en) | 2008-03-03 | 2016-01-19 | University Of Miami | Allogeneic cancer cell-based immunotherapy |
| US10046047B2 (en) | 2015-02-06 | 2018-08-14 | Heat Biologics, Inc. | Vector co-expressing vaccine and costimulatory molecules |
| US10758611B2 (en) | 2015-02-06 | 2020-09-01 | Heat Biologics, Inc. | Vector co-expressing vaccine and costimulatory molecules |
| US10780161B2 (en) | 2015-02-06 | 2020-09-22 | Heat Biologics, Inc. | Vector co-expressing vaccine and costimulatory molecules |
| US10568948B2 (en) | 2015-05-13 | 2020-02-25 | Agenus Inc. | Vaccines for treatment and prevention of cancer |
| US11666649B2 (en) | 2016-10-11 | 2023-06-06 | University Of Miami | Vectors and vaccine cells for immunity against Zika virus |
| US11548930B2 (en) | 2017-04-04 | 2023-01-10 | Heat Biologics, Inc. | Intratumoral vaccination |
| US11065317B2 (en) | 2018-04-26 | 2021-07-20 | Agenus Inc. | Heat shock protein-binding peptide compositions and methods of use thereof |
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