CA2368855A1 - Differentiation of monocytes into functional dendritic cells - Google Patents
Differentiation of monocytes into functional dendritic cells Download PDFInfo
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- CA2368855A1 CA2368855A1 CA002368855A CA2368855A CA2368855A1 CA 2368855 A1 CA2368855 A1 CA 2368855A1 CA 002368855 A CA002368855 A CA 002368855A CA 2368855 A CA2368855 A CA 2368855A CA 2368855 A1 CA2368855 A1 CA 2368855A1
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- 210000004443 dendritic cell Anatomy 0.000 title claims abstract 16
- 230000004069 differentiation Effects 0.000 title claims abstract 5
- 239000003795 chemical substances by application Substances 0.000 claims abstract 54
- 201000010099 disease Diseases 0.000 claims abstract 50
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract 50
- 238000000034 method Methods 0.000 claims abstract 42
- 239000000203 mixture Substances 0.000 claims abstract 34
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- 210000004027 cell Anatomy 0.000 claims abstract 16
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- 239000008280 blood Substances 0.000 claims abstract 12
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- 239000011230 binding agent Substances 0.000 claims abstract 11
- 210000000612 antigen-presenting cell Anatomy 0.000 claims abstract 8
- 108091092356 cellular DNA Proteins 0.000 claims abstract 2
- 230000001939 inductive effect Effects 0.000 claims abstract 2
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- 229940027041 8-mop Drugs 0.000 claims 4
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- 102000004457 Granulocyte-Macrophage Colony-Stimulating Factor Human genes 0.000 claims 4
- 108090000978 Interleukin-4 Proteins 0.000 claims 4
- 206010025323 Lymphomas Diseases 0.000 claims 4
- QXKHYNVANLEOEG-UHFFFAOYSA-N Methoxsalen Chemical group C1=CC(=O)OC2=C1C=C1C=COC1=C2OC QXKHYNVANLEOEG-UHFFFAOYSA-N 0.000 claims 4
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- 210000003719 b-lymphocyte Anatomy 0.000 claims 2
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- 230000003612 virological effect Effects 0.000 claims 2
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- A61K41/0057—Photodynamic therapy with a photosensitizer, i.e. agent able to produce reactive oxygen species upon exposure to light or radiation, e.g. UV or visible light; photocleavage of nucleic acids with an agent
- A61K41/0066—Psoralene-activated UV-A photochemotherapy (PUVA-therapy), e.g. for treatment of psoriasis or eczema, extracorporeal photopheresis with psoralens or fucocoumarins
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- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
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- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
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Abstract
A method for inducing differentiation of monocytes contained in an extracorporeal quantity of a subject's blood into functional dendritic antigen presenting cells is provided. The monocytes are first treated by exposure to physical perturbation, irradiation in the presence of a photoactivatable agent capable of forming photoadducts with cellular DNA components, and/or treatment with a DNA binding agent. The treated monocytes are then incubated for a period of time sufficient to maximize the number of functional dendritic cells in the treated cell population. Functional dendritic cells generated from induced monocytes are incubated together with disease effector agents to enhance the presentation of at least one disease-causing antigen expressed by the disease effector agents. Compositions including dendritic cells derived from induced monocytes and compositions including such dendritic cells incubated with disease effector agents are also provided.
Claims (63)
1. A method for inducing differentiation of monocytes contained in an extracorporeal quantity of a subject's blood into functional dendritic antigen presenting cells, said method comprising the steps of:
(a) treating the monocytes by at least one of the following: (1) exposing the monocytes to physical perturbation, (2) irradiating the monocytes in the presence of a photoactivatable agent capable of forming photoadducts with cellular DNA components, and (3) treating the monocytes with a DNA binding agent; and (b) incubating the treated monocytes for a period of time sufficient to maximize the number of functional dendritic cells.
(a) treating the monocytes by at least one of the following: (1) exposing the monocytes to physical perturbation, (2) irradiating the monocytes in the presence of a photoactivatable agent capable of forming photoadducts with cellular DNA components, and (3) treating the monocytes with a DNA binding agent; and (b) incubating the treated monocytes for a period of time sufficient to maximize the number of functional dendritic cells.
2. The method of claim 1, wherein prior to step (a) the method further comprises the step of:
separating the monocytes from the extracorporeal quantity of the subject's blood by subjecting the quantity of blood to a leukapheresis process.
separating the monocytes from the extracorporeal quantity of the subject's blood by subjecting the quantity of blood to a leukapheresis process.
3. The method of claim 2, wherein the monocytes are incubated for a period of from about 6 to about 48 hours.
4. The method of claim 3, wherein the monocytes are incubated for a period of from about 12 to about 24 hours.
5. The method of claim 3, wherein the monocytes are irradiated in the presence of the photoactivatable agent.
6. The method of claim 6, wherein the photoactivatable agent is 8-MOP.
7. The method of claim 3, wherein the monocytes are exposed to the DNA binding agent.
8. The method of claim 3, wherein the treated monocytes are incubated together with at least one of GM-CSF and IL-4.
9. The method of claim 3, wherein the monocytes are incubated in a container which does not leach substantial amounts of plasticizer and which is sufficiently porous to permit exchange of gases.
10. The method of claim 3, wherein the treated monocytes are incubated together with at least one selected antigen to be processed and presented by the dendritic cells.
11. The method of claim 10, wherein the at least one antigen is expressed on the surface of a disease effector agent.
12. The method of claim 11, wherein the disease effector agent is selected from the group consisting of disease-causing cells and microbes.
13. A composition comprising functional dendritic antigen presenting cells derived from monocytes which have been incubated following their treatment by at least one of: (1) exposure to physical perturbation, (2) irradiation in the presence of a photoactivatable agent capable of forming photoadducts with cellular components, and (3) treatment with a DNA binding agent.
14. The composition of claim 13, wherein the treated monocytes have been incubated for a period of time sufficient to maximize the number of functional dendritic cells present in the composition.
15. The composition of claim 14, wherein the treated monocytes have been incubated for a period of from about 6 to about 48 hours.
16. The composition of claim 15, wherein the monocytes have been incubated for a period of from about 12 to about 24 hours.
17. The composition of claim 14, wherein the monocytes have been irradiated in the presence of the photoactivatable agent.
18. The composition of claim 17, wherein the photoactivatable agent is 8-MOP.
19. The composition of claim 14, wherein the monocytes have been exposed to the DNA binding agent.
20. The composition of claim 14, further comprising at least one of GM-CSF and IL-4.
21. The composition of claim 14 further comprising at least one selected antigen for presentation by the dendritic cells.
22. The composition of claim 21, wherein the at least one antigen is expressed on the surface of a disease effector agent.
23. The method of claim 22, wherein the disease effector agent is selected from the group consisting of disease-causing cells and microbes.
24. A packaged preparation comprising:
a composition including functional dendritic antigen presenting cells derived from monocytes which have been incubated following their treatment by at least one of exposure to physical perturbation, irradiation in the presence of a photoactivatable agent capable of forming photoadducts with cellular components, and treatment with a DNA binding agent; and a container which does not leach substantial amounts of plasticizer and which is sufficiently porous to permit exchange of gases for storing the composition.
a composition including functional dendritic antigen presenting cells derived from monocytes which have been incubated following their treatment by at least one of exposure to physical perturbation, irradiation in the presence of a photoactivatable agent capable of forming photoadducts with cellular components, and treatment with a DNA binding agent; and a container which does not leach substantial amounts of plasticizer and which is sufficiently porous to permit exchange of gases for storing the composition.
25. The packaged preparation of claim 24, wherein the treated monocytes have been incubated for a period of time sufficient to maximize the number of functional dendritic cells present in the composition.
26. The packaged preparation of claim 25, wherein the composition further includes at least one of GM-CSF and IL-4.
27. The packaged preparation of claim 25, wherein the composition further includes at least one selected antigen for presentation by the dendritic cells.
28. A method of enhancing the presentation of disease associated antigens, said method comprising the steps of:
(a) treating disease effector agents capable of expressing at least one disease associated antigen to one of: render the agents apoptotic and inactivate the agents;
(b) treating monocytes contained in an extracorporeal quantity of a subject's blood by at least one of the following: (1) exposing the monocytes to physical perturbation, (2) irradiating the monocytes in the presence of a photoactivatable agent capable of forming photoadducts with cellular components, and (3) treating the monocytes with a DNA binding agent; and (c) incubating the treated disease effector agents and the treated monocytes together for a period of time sufficient to induce differentiation of the monocytes into functional dendritic antigen presenting cells and to optimize processing and presentation of the disease associated antigens by the dendritic cells.
(a) treating disease effector agents capable of expressing at least one disease associated antigen to one of: render the agents apoptotic and inactivate the agents;
(b) treating monocytes contained in an extracorporeal quantity of a subject's blood by at least one of the following: (1) exposing the monocytes to physical perturbation, (2) irradiating the monocytes in the presence of a photoactivatable agent capable of forming photoadducts with cellular components, and (3) treating the monocytes with a DNA binding agent; and (c) incubating the treated disease effector agents and the treated monocytes together for a period of time sufficient to induce differentiation of the monocytes into functional dendritic antigen presenting cells and to optimize processing and presentation of the disease associated antigens by the dendritic cells.
29. The method of claim 28, wherein the treated disease effector agents and the treated monocytes are incubated together for a period of from about 6 to about 40 hours.
30. The method of claim 29, wherein the treated disease effector agents and the monocytes are incubated together for a period of from about 12 to about 24 hours.
31. The method of claim 28, wherein the disease effector agents are contained in the extracorporeal quantity of the subject's blood.
32. The method of claim 28, wherein the disease effector agents are derived from an exogenous source.
33. The method of claim 31, wherein prior to step (a) the method further comprises the step of:
separating the disease effector agents and the monocytes from the extracorporeal quantity of the subject's blood by subjecting the quantity of blood to a leukapheresis process.
separating the disease effector agents and the monocytes from the extracorporeal quantity of the subject's blood by subjecting the quantity of blood to a leukapheresis process.
34. The method of claim 28, wherein the disease effector agents are selected from the group consisting of disease-causing cells and microbes.
35. The method of claim 34 wherein the disease-causing cells selected from the group consisting of T-cells, B-cells and macrophages.
36. The method of claim 35, wherein the T-cells include lymphoma cells.
37. The method of claim 36, wherein the lymphoma cells include cutaneous T-cell lymphoma cells.
38. The method of claim 28, wherein steps (a) and (b) are performed simultaneously by irradiating the disease effector agents and the monocytes with a photoactivatable agent capable of forming photoadducts with DNA and cell proteins.
39. The method of claim 38, wherein the photoactivatable agent is 8-MOP.
40. The method of claim 28, wherein the disease associated antigen is selected from the group consisting of viral antigens, fungal antigens, bacterial antigens, transplant antigens and tumor specific antigens.
41. The method of claim 40, wherein the tumor specific antigen is a peptide derived from a T-cell antigen-binding cell surface receptor.
42. The method of claim 28, wherein the disease effector agents and the monocytes are incubated together with at least one of GM-CSF, IL-4, TNF-alpha, and IL-12.
43. The method of claim 28, wherein the disease effector agents and the monocytes are incubated together in a container which does not leach substantial amounts of plasticizer.
44. The method of claim 28, further including the step of:
administering the incubated disease effector agents and the dendritic cells to the subject to elicit an immune response.
administering the incubated disease effector agents and the dendritic cells to the subject to elicit an immune response.
45. The method of claim 44, wherein the incubated disease effector agents and the dendritic cells are administered to the subject in at least one of the presence of and in combination with an immunomodulatory agent.
46. A composition of co-incubated populations comprising:
a first population including disease effector agents which express at least one disease associated antigen; and a second population including functional dendritic antigen presenting cells derived from monocytes which have been treated by at least one of (1) exposure to physical perturbation, (2) irradiation in the presence of a photoactivatable agent capable of forming photoadducts with cellular components, and (3) treatment with a DNA binding agent.
a first population including disease effector agents which express at least one disease associated antigen; and a second population including functional dendritic antigen presenting cells derived from monocytes which have been treated by at least one of (1) exposure to physical perturbation, (2) irradiation in the presence of a photoactivatable agent capable of forming photoadducts with cellular components, and (3) treatment with a DNA binding agent.
47. The composition of claim 46, wherein the first and second populations have been co-incubated for a period of from about 6 to about 40 hours.
48. The composition of claim 47, wherein the first and second populations have been co-incubated for a period of from about 12 to about 24 hours.
49. The composition of claim 46, wherein the disease effector agents are selected from the group consisting of disease-causing cells and microbes.
50. The composition of claim 49, wherein the disease-causing cells are selected from the group consisting of T-cell, B-cells and macrophages.
51. The composition of claim 50, wherein the T-cells include lymphoma cells.
52. The composition of claim 51, wherein the lymphoma cells include cutaneous T-cell lymphoma cells.
53. The composition of claim 46, wherein the disease effector agents and the monocytes have been treated with a photoactivatable agent.
54. The composition of claim 53, wherein the photoactivatable agent is 8-MOP.
55. The composition of claim 46, wherein the disease effector cells and the monocytes have been treated with a DNA binding agent.
56. The composition of claim 46, wherein the monocytes are separated from an extracorporeal quantity of a subject's blood.
57. The composition of claim 56, wherein the disease effector agents are one of contained in the extracorporeal quantity of the subject's blood and derived from an exogenous source.
58. The composition of claim 46, wherein the disease associated antigen is selected from the group consisting of viral antigens, fungal antigens, bacterial antigens, transplant antigens, and tumor specific antigens.
59. The composition of claim 46, further including at least one immunomodulatory agent.
60. A packaged composition of co-incubated populations comprising:
a first population including disease effector agents which express at least one disease associated antigen;
a second population including functional dendritic antigen presenting cells derived from monocytes which have been treated by at least one of: (1) exposure to physical perturbation, (2) irradiation in the presence of a photoactivatable agent capable of forming photoadducts with cellular components, and (3) treatment with a DNA binding agent; and a container which does not leach substantial amounts of plasticizer and which is sufficiently porous to permit exchange of gases for storing the composition.
a first population including disease effector agents which express at least one disease associated antigen;
a second population including functional dendritic antigen presenting cells derived from monocytes which have been treated by at least one of: (1) exposure to physical perturbation, (2) irradiation in the presence of a photoactivatable agent capable of forming photoadducts with cellular components, and (3) treatment with a DNA binding agent; and a container which does not leach substantial amounts of plasticizer and which is sufficiently porous to permit exchange of gases for storing the composition.
61. A method of providing a vaccine against disease effector agents capable of expressing at least one disease associated antigen; said method comprising the steps of:
(a) treating the disease effector agents to one of: render the agents apoptotic and inactivate the agents;
(b) treating monocytes contained in an extracorporeal quantity of a subject's blood by at least one of the following: (1) exposing the monocytes to physical perturbation, (2) irradiating the monocytes in the presence of a photoactivatable agent capable of forming photoadducts with cellular components, and (3) treating the monocytes with a DNA binding agent;
(c) incubating the treated disease effector agents and the treated monocytes together for a period of time sufficient to induce differentiation of the monocytes into functional dendritic antigen presenting cells and to optimize processing and presentation of the disease associated antigens by the dendritic cells;
and (d) administering the incubated disease effector agents and the dendritic cells to the subject to vaccinate the subject against the disease effector agents.
(a) treating the disease effector agents to one of: render the agents apoptotic and inactivate the agents;
(b) treating monocytes contained in an extracorporeal quantity of a subject's blood by at least one of the following: (1) exposing the monocytes to physical perturbation, (2) irradiating the monocytes in the presence of a photoactivatable agent capable of forming photoadducts with cellular components, and (3) treating the monocytes with a DNA binding agent;
(c) incubating the treated disease effector agents and the treated monocytes together for a period of time sufficient to induce differentiation of the monocytes into functional dendritic antigen presenting cells and to optimize processing and presentation of the disease associated antigens by the dendritic cells;
and (d) administering the incubated disease effector agents and the dendritic cells to the subject to vaccinate the subject against the disease effector agents.
62. The method of claim 61, wherein the disease effector agents are selected from the group consisting of disease-causing cells and microbes.
63. The method of claim 61, wherein the disease effector agents are one of: contained in the extracorporeal quantity of the subject's blood and derived from an exogenous source.
Applications Claiming Priority (4)
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US10/066,021 US20020114793A1 (en) | 1999-04-20 | 2002-01-31 | Methods for inducing the differentiation of monocytes into functional dendritic cells and immunotherapeutic compositions including such dendritic cells |
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EP (2) | EP1176986B1 (en) |
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CA (2) | CA2368855C (en) |
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AU782391B2 (en) * | 1999-04-20 | 2005-07-21 | Richard Leslie Edelson | Differentiation of monocytes into functional dendritic cells |
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US8313945B2 (en) | 1999-04-20 | 2012-11-20 | Yale University | Methods for inducing the differentiation of blood monocytes into functional dendritic cells |
US20050084966A1 (en) * | 1999-04-20 | 2005-04-21 | Edelson Richard L. | Methods for inducing the differentiation of blood monocytes into functional dendritic cells |
US20050158856A1 (en) * | 1999-04-20 | 2005-07-21 | Edelson Richard L. | Methods for producing functional antigen presenting dendritic cells using biodegradable microparticles for delivery of antigenic materials |
US7109031B2 (en) * | 1999-04-20 | 2006-09-19 | Yale University | Methods for inducing the differentiation of monocytes into functional dendritic cells and immunotherapeutic compositions including such dendritic cells |
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WO2005027841A2 (en) * | 2003-09-16 | 2005-03-31 | University Of North Carolina At Chapel Hill | Cells, compositions and methods for repressing b cell autoantibody secretion and for treating autoimmune disease |
AU2004294243B2 (en) * | 2003-12-05 | 2011-02-17 | Hopital Maisonneuve-Rosemont | Immunologic compounds for prevention, protection, prophylaxis or treatment of immunological disorders, infections and cancer |
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KR20200072566A (en) | 2005-04-08 | 2020-06-22 | 코이뮨, 인크. | Dendritic cell compositions and methods |
JP5032792B2 (en) | 2006-05-22 | 2012-09-26 | 浜松ホトニクス株式会社 | Cell sorter |
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WO2011046832A2 (en) | 2009-10-12 | 2011-04-21 | The United States Of America, As Represented By The Secretary, Department Of Health & Human Services | Granulysin in immunotherapy |
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CN113976052B (en) * | 2021-11-03 | 2022-06-10 | 健进制药有限公司 | Multivesicular liposome preparation system and preparation method thereof |
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2000
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US6607722B2 (en) | 2003-08-19 |
AU782391B2 (en) | 2005-07-21 |
CA2474571A1 (en) | 2003-08-07 |
EP1478735A1 (en) | 2004-11-24 |
EP1478735A4 (en) | 2006-08-02 |
US6524855B2 (en) | 2003-02-25 |
WO2003064632A1 (en) | 2003-08-07 |
US20010053355A1 (en) | 2001-12-20 |
WO2000062818A1 (en) | 2000-10-26 |
EP1176986A4 (en) | 2004-06-16 |
JP2005515781A (en) | 2005-06-02 |
CA2368855C (en) | 2012-05-29 |
EP1176986B1 (en) | 2018-07-04 |
EP1176986A1 (en) | 2002-02-06 |
US20020004044A1 (en) | 2002-01-10 |
US20020114793A1 (en) | 2002-08-22 |
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