CA2407680A1 - Dendritic cell co-stimulator molecules - Google Patents

Dendritic cell co-stimulator molecules Download PDF

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CA2407680A1
CA2407680A1 CA002407680A CA2407680A CA2407680A1 CA 2407680 A1 CA2407680 A1 CA 2407680A1 CA 002407680 A CA002407680 A CA 002407680A CA 2407680 A CA2407680 A CA 2407680A CA 2407680 A1 CA2407680 A1 CA 2407680A1
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cells
polypeptide
cell
subject
seq
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CA2407680C (en
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Drew M. Pardoll
Haruo Tsuchiya
Kevin S. Gorski
Su-Yi Tseng
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Johns Hopkins University
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Drew M. Pardoll
Haruo Tsuchiya
Kevin S. Gorski
Su-Yi Tseng
The Johns Hopkins University
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    • 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
    • A61K39/395—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
    • A61K39/39533—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum against materials from animals
    • A61K39/39558—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum against materials from animals against tumor tissues, cells, antigens
    • 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
    • C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
    • C12N15/09—Recombinant DNA-technology
    • C12N15/11—DNA or RNA fragments; Modified forms thereof; Non-coding nucleic acids having a biological activity
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • 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
    • A61K39/463—Cellular immunotherapy characterised by recombinant expression
    • A61K39/4632—T-cell receptors [TCR]; antibody T-cell receptor constructs
    • 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
    • A61K39/464838—Viral antigens
    • 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
    • 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
    • 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
    • A61P37/06—Immunosuppressants, e.g. drugs for graft rejection
    • 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
    • C07K14/70503—Immunoglobulin superfamily
    • C07K14/70532—B7 molecules, e.g. CD80, CD86
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
    • C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
    • C07K16/28—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
    • C07K16/2803—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against the immunoglobulin superfamily
    • C07K16/2827—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against the immunoglobulin superfamily against B7 molecules, e.g. CD80, CD86
    • 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
    • A61K2039/505—Medicinal preparations containing antigens or antibodies comprising antibodies
    • 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
    • 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
    • A61K2039/555—Medicinal preparations containing antigens or antibodies characterised by a specific combination antigen/adjuvant
    • A61K2039/55511—Organic adjuvants
    • A61K2039/55516—Proteins; Peptides
    • 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
    • A61K2039/57—Medicinal preparations containing antigens or antibodies characterised by the type of response, e.g. Th1, Th2
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2239/00—Indexing codes associated with cellular immunotherapy of group A61K39/46
    • A61K2239/38—Indexing codes associated with cellular immunotherapy of group A61K39/46 characterised by the dose, timing or administration schedule
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2319/00—Fusion polypeptide
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2319/00—Fusion polypeptide
    • C07K2319/30—Non-immunoglobulin-derived peptide or protein having an immunoglobulin constant or Fc region, or a fragment thereof, attached thereto

Abstract

A costimulatory protein molecule, B7-DC, which is a member of the B7 family, is described as is DNA coding therefor and expression vectors comprising thi s DNA. B7-DC protein, fragments, fusion polypeptides/proteins and other functional derivatives, and transformed cells expressing B7-DC are useful in vaccine compositions and methods. Compositions and methods are disclosed for inducing potent T cell mediated responses that can be harnessed for anti-tum or and anti-viral immunity.

Claims (68)

1.~An isolated nucleic acid molecule that encodes a mammalian protein termed B7-DC that is selectively expressed on dendritic cells as compared to activated macrophages.
2. ~The nucleic acid molecule of claim 1 that comprises a nucleotide sequence selected from SEQ ID NO: 1 or SEQ ID NO:5.
3. ~An isolated nucleic acid molecule that hybridizes with the nucleic acid molecule of claim 1 or 2 under stringent hybridization conditions.
4. ~The nucleic acid molecule of claim 2 that comprises the nucleotide sequence SEQ ID NO:1.
5. ~The nucleic acid molecule of any of claims 1-4 that encodes a protein having an amino acid sequence selected from SEQ ID NO:2 and SEQ ID NO:4 or encodes a biologically active fragment, homologue or other functional derivative of said protein.
6. ~The nucleic acid molecule of claim 6 that encodes said protein having the sequence SEQ ID NO:2 or encodes said biologically active fragment, homologue or other functional derivative of SEQ ID NO:2.
7. ~A fragment of the nucleic acid molecule of any of claims 5 or 6 that encodes all or part of the extracellular domain of said B7-DC protein.
8. ~The nucleic acid molecule of claim 5 that encodes a B7-DC fusion polypeptide, which molecule comprises:
(a) ~a first nucleic acid sequence encoding a first polypeptide that is all or a part of a B7-DC protein SEQ ID NO: 2 or SEQ ID NO:4;
(b) ~optionally, fused in frame with the first nucleic acid sequence, a linker nucleic acid sequence encoding a linker peptide; and (c) ~a second nucleic acid sequence that is linked in frame to said first nucleic acid sequence or to said linker nucleic acid sequence and that encodes a second polypeptide.
9. ~The nucleic acid molecule of claim 8 wherein said second polypeptide consists of one or more domains of an Ig heavy chain constant region.
10. ~The nucleic acid molecule of claim 11 wherein said second polypeptide consists of two domains of a human IgG constant region.
11. ~An expression vector comprising the nucleic acid of any of claims 1-10 operatively linked to:
(a) a promoter and (b) optionally, additional regulatory sequences that regulate expression of said nucleic acid in a eukaryotic cell.
12. ~The expression vector of claim 11 which is a plasmid.
13. ~The expression vector of claim 11 which is a viral vector.
14. ~A vector composition comprising (a) ~a first recombinant expression vector having incorporated in its nucleic acid a nucleotide sequence encoding an antigen of interest against which an immune response is to be induced; and (b) ~a second recombinant expression vector having incorporated in its nucleic acid one or more nucleotide sequences encoding a co-stimulator polypeptide, at least one of which co-stimulator polypeptides is B7-DC, or is a biologically active fragment, homologue or other functional derivative thereof, wherein the expression vectors are able to co-infect or co-transfect a host cell resulting in co-expression of the antigen and the costimulator polypeptide, fragment, homologue or derivative.
15. ~The vector of claim 14 wherein said second vector comprises SEQ ID NO:1 or SEQ ID NO:5.
16. ~The vector of claim 14 or 15 wherein said second vector comprises SEQ ID
NO:1.
17. ~A cell transformed or transfected with the nucleic acid molecule of any of claims 1-
18. ~A cell transformed or transfected with the expression vector of any of claims claim 1-16.
19. The cell of claim 19 which is a mammalian cell.
20. The cell of claim 19 which is a human cell.
21. The cell of claim 19 which is a dendritic cell or a progenitor thereof.
22. The cell of claim 19 which is a tumor cell.
23. An isolated mammalian tumor cell transfected with an exogenous nucleic acid molecule encoding a mammalian B7-DC protein or a biologically active fragment, homologue or other functional derivative thereof, such that when said protein, fragment, homologue or derivative is expressed by said tumor cell, and said tumor cell is contacted with T cells (i) said B7-DC protein, fragment, homologue or derivative binds to said T
cells; and (ii) said tumor cell costimulates said T cells to proliferate and/or to produce and secrete cytokines.
24. The tumor cell of claim 23 wherein said exogenous nucleic acid molecule comprises SEQ ID NO:1, SEQ ID NO:5 or a fragment of said sequence.
25. A polypeptide that is selectively expressed on dendritic cells as compared to activated macrophages and has the following functional properties:
(a) binds to a binding partner on T cells; and (b) costimulates T cells to proliferate and/or to produce and secrete cytokines.
26. The polypeptide, fragment, homologue or functional derivative of claim 25 encoded by a nucleic acid molecule having the sequence SEQ ID NO:1 or SEQ ID
NO:5, or a fragment, homologue or equivalent of said nucleic acid molecule.
27. The polypeptide of claim 26 having the amino acid sequence SEQ ID N0:2 or SEQ ID NO:4, or a fragment, homologue or equivalent of said polypeptide.
28. A polypeptide or a biologically active fragment, homologue or other functional derivative of said polypeptide produced by recombinant expression of the nucleic acid of any of claims 1 - 10.
29. The polypeptide of any of claims 25-28 comprising the extracellular domain of the B7-DC protein, which domain comprises amino acid residues 26-221 of SEQ ID
NO:2 or SEQ ID NO:4, or a co-stimulatory fragment, homologue or other functional derivative of said domain.
30. The polypeptide of any of claims 25-28 consisting essentially of the extracellular domain of B7-DC which domain includes amino acid residues 26-221of SEQ ID NO:2 or SEQ
ID NO:4, or a co-stimulatory fragment, homologue or other functional derivative of residues 26-221.
31. A B7-DC fusion polypeptide having a first fusion partner comprising all or a part of a B7-DC protein which (i) is fused directly to a second polypeptide or, (ii) optionally, is fused to a linker peptide sequence that is fused to said second polypeptide.
32. A B7-DC fusion polypeptide comprising the polypeptide of any of claims claim 25-30 fused to a second polypeptide.
33. The fusion polypeptide of claim 32, that binds to a binding partner molecule on T
cells and co-stimulates said T cells in the presence of an adequate stimulus to the T cell receptor.
34. The fusion polypeptide of claim 33 wherein said binding partner molecule is PD-1.
35. The fusion polypeptide of any of claims 31-33 wherein said second polypeptide is one or more domains of an Ig heavy chain constant region.
36. The fusion polypeptide of any of claims 31-35 wherein said first fusion partner comprises amino acids 26-221 of SEQ ID NO:2 or of SEQ ID NO:4, or a co-stimulatory fragment, homologue or other functional derivative thereof.
37. The fusion polypeptide of claim 36 wherein said first fusion partner comprises amino acids 26-221 of SEQ ID NO:2, or a co-stimulatory fragment, homologue or other functional derivative thereof.
38. The fusion polypeptide of claim 35 wherein said polypeptide has an amino acid sequence corresponding to the hinge, CH2 and CH3 regions of a human immunoglobulin C.gamma.1 chain.
39. A dimeric or trimeric fusion polypeptide which is a tandemly linked dimer or trimer of the fusion polypeptide of any of claims 31-38.
40. The fusion polypeptide of any of claims 31 - 38, comprising a linear multimer of two or more repeats of monomers of said first fusion partner linked end to end, directly or with a linker sequences present between said monomer repeats.
41. An antibody that is specific for an epitope of a B7-DC protein, which epitope is not present in a known member of a B7 family protein.
42. The antibody of claim 41 wherein said epitope is a linear or conformational epitope of a polypeptide of SEQ ID NO:2 or SEQ ID NO:4.
43. The antibody of claim 42 wherein said epitope is a linear or conformational epitope of a polypeptide of SEQ ID NO:2.
44. The antibody of any of claims 41-42 that is a monoclonal antibody.
45. The antibody of claim 43 that is a human or humanized monoclonal antibody.
46. A method of identifying or quantitating cells expressing a B7-DC
polypeptide on their surface in a cell population, comprising (a) contacting cells of said population with the antibody of any of claims 41-45, so that said antibody binds to cells expressing said epitope;
(b) assessing the presence of, or quantitating the number of, cells to which said antibody is bound.
47. A method of isolating cells expressing a B7-DC polypeptide on their surface from a cell population, comprising (a) contacting cells of said population with the antibody of any of claims 41-45, so that said antibody binds to cells expressing said epitope;

(b) positively selecting cells to which said antibody has bound or negatively selecting cells to which said antibody has not bound, thereby isolating said cells.
48. A method of detecting the presence or quantitating a B7-DC polypeptide, fragment or homologue in a sample, comprising the steps of:
(a) contacting the sample with the antibody of any of claims 41-45, such that the antibody binds to any polypeptides or fragments bearing said epitope;
(b) detecting the presence of, or quantitating the polypeptides or fragments bound to said antibody.
49. A method of inducing or increasing the expression of a B7-DC polypeptide in an antigen presenting cell or a progenitor thereof to increase the ability of said cell to co-stimulate T cells in vitro or in vivo in the presence of an adequate stimulus to the T
cell receptor, comprising transforming or transfecting said antigen presenting cell or progenitor cell with the expression vector of any of claims 11-13, such that said expression of the B7-DC polypeptide is induced or increased on said cells.
50. A method of inducing or increasing the expression of a B7-DC polypeptide in an antigen presenting cell or a progenitor thereof to increase the ability of said cell to co-stimulate T cells in vitro or in vivo in the presence of an adequate stimulus to the T
cell receptor, comprising transforming or transfecting said antigen presenting cell or progenitor cell with the expression vector of any of claims 11-13, such that said expression of the B7-DC polypeptide is induced or increased on said cells.
51. The method of claim 49 or 50 wherein said antigen presenting cells are dendritic cells and said progenitors are dendritic cell progenitors.
52. A method for increasing the T cell response of a mammalian subject to antigenic stimulation, comprising administering to said subject an effective amount of cells according to any of claims 17-24, in conjunction with an antigen, wherein said cells are effective to increase the T cell response of said subject to said antigenic stimulation.
53. A method for increasing the T cell response of a mammalian subject to antigenic stimulation with a tumor-associated antigen, comprising administering to said subject an effective amount of tumor cells according to any of claims 22 -24, wherein said tumor cells express said antigen, said administration of said tumor cells being effective to increase the T cell response of said subject to said tumor antigen stimulation.
54. A method for increasing the T cell response of a mammalian subject to antigenic stimulation, comprising administering to said subject an effective amount of a polypeptide, fragment, homologue or functional derivative according to any of claims 25-30 in conjunction with an antigen, wherein the administration of said polypeptide is effective to increase the T cell response of said subject to said antigenic stimulation.
55. A method for increasing the T cell response of a mammalian subject to antigenic stimulation, comprising administering to said subject an effective amount of a fusion polypeptide according to any of claims 31-40, in conjunction with an antigen, wherein the administration of said polypeptide is effective to increase the T cell response of said subject to said antigenic stimulation.
56. A method for inhibiting a T cell response of a mammalian subject to antigenic stimulation, comprising administering to said subject an effective amount of an antibody according to any of claims 41-45, wherein the administration of said antibody is effective to block stimulation of T cells or to eliminate antigen-reactive T cells, thereby inhibiting the T cell response.
57. The method of claim 56 wherein said T cell response is directed to a tissue transplant or to an autoantigen such that said method inhibits transplant rejection or an autoimmune reaction.
58. A method for increasing the immune response of a mammalian subject to antigenic stimulation comprising:
(a) obtaining T cells from (i) said subject, (ii) an immunologically compatible donor for said subject, or (iii) an immunologically compatible or acceptable cultured cell line;

(b) contacting said T cells ex vivo with an effective amount of cells according to any of claim 17-24, wherein said contacting is effective to increase the response of said T cells to antigenic stimulation; and (c) administering said T cells of step (b) to said subject, thereby increasing said immune response of said subject.
59. A method for increasing the immune response of a mammalian subject to antigenic stimulation comprising:

(a) obtaining T cells from (i) said subject, (ii) an immunologically compatible donor for said subject, or (iii) an immunologically compatible or acceptable cultured cell line;

(b) contacting said T cells ex vivo with an effective amount of cells according to any of claims 17-24, wherein said contacting is effective to increase the response of said T cells to antigenic stimulation; and (c) administering said T cells of step (b) to said subject, thereby increasing said immune response of said subject.
60. A method for increasing the immune response of a mammalian subject to antigenic stimulation comprising:

(a) obtaining T cells from (i) said subject, (ii) an immunologically compatible donor for said subject, or (iii) an immunologically compatible or acceptable cultured cell line;

(b) contacting said T cells ex vivo with an effective amount of the polypeptide, fragment, homologue or functional derivative of any of claims 25-30, wherein said contacting is effective to increase the response of said T cells to antigenic stimulation; and (c) administering said T cells of step (b) to said subject, thereby increasing said immune response of said subject.
61. A method for increasing the immune response of a mammalian subject to antigenic stimulation comprising:

(a) obtaining T cells from (i) said subject, (ii) an immunologically compatible donor for said subject, or (iii) an immunologically compatible or acceptable cultured cell line;

(b) contacting said T cells ex vivo with an effective amount of a the fusion polypeptide of any of claims 31-40, wherein said contacting is effective to increase the response of said T cells to antigenic stimulation; and (c) administering said T cells of step (b) to said subject, thereby increasing said immune response of said subject.
62. A vaccine composition useful for inducing a protective immune response against an antigen associated with a pathogenic cell or microorganism, comprising (a) the transformed or transfected cells of any of claims 17-24 which optionally express said antigen;

(b) if the cells of (a) do not express said antigen, an additional source of said antigen;

(c) optionally, a general immunostimulatory agent or adjuvant; and (d) a pharmaceutically and immunologically acceptable excipient or carrier for (a), b) and (c).
63. A vaccine composition useful for inducing a protective immune response against an antigen associated with a pathogenic cell or microorganism, comprising (a) a source of antigen to which an immune response is desired;

(b) the polypeptide, fragment, homologue or functional derivative of any of claims 25-30;

(c) optionally, a general immunostimulatory agent or adjuvant; and (d) a pharmaceutically and immunologically acceptable excipient or carrier for (a), b) and (c).
64. A vaccine composition useful for inducing a protective immune response against an antigen associated with a pathogenic cell or microorganism, comprising (a) a source of antigen to which an immune response is desired;

(b) the fusion polypeptide of any of claims 31-40;

(c) optionally, a general immunostimulatory agent or adjuvant; and (d) a pharmaceutically and immunologically acceptable excipient or carrier for (a), b) and (c).
65. A co-stimulatory composition for use with an antigen or a vaccine to increase the immunogenicity of the antigen or vaccine, comprising:

(a) the polypeptide, fragment, homologue or functional derivative of any of claims 25-30; and (b) a pharmaceutically and immunologically acceptable excipient or carrier.
66. A co-stimulatory composition for use with an antigen or a vaccine to increase the immunogenicity of the antigen or vaccine, comprising:

(a) the fusion polypeptide of any of claims 31-40; and (b) a pharmaceutically and immunologically acceptable excipient or carrier.
67. A method for inducing or enhancing an immune response to an antigen in a mammalian subject comprising administering to said subject an effective amount of the vaccine composition of any of claims 62-64.
68. A method for potentiating an immune response to an antigen or a vaccine in a mammalian subject, comprising administering to said subject, in combination with said antigen or vaccine, the costimulatory composition of claim 65 or 66.
CA2407680A 2000-04-28 2001-04-27 Dendritic cell co-stimulator molecules Expired - Fee Related CA2407680C (en)

Applications Claiming Priority (7)

Application Number Priority Date Filing Date Title
US20058000P 2000-04-28 2000-04-28
US60/200,580 2000-04-28
US24016900P 2000-10-13 2000-10-13
US60/240,169 2000-10-13
US09/794,210 2001-02-28
US09/794,210 US7030219B2 (en) 2000-04-28 2001-02-28 B7-DC, Dendritic cell co-stimulatory molecules
PCT/US2001/013430 WO2001083750A2 (en) 2000-04-28 2001-04-27 Dendritic cell co-stimulator molecules

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CA2407680A1 true CA2407680A1 (en) 2001-11-08
CA2407680C CA2407680C (en) 2012-02-21

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EP (1) EP1280900B8 (en)
JP (2) JP4987208B2 (en)
KR (1) KR100884766B1 (en)
CN (1) CN102199216A (en)
AT (1) ATE437228T1 (en)
AU (2) AU2001255700C1 (en)
CA (1) CA2407680C (en)
DE (1) DE60139311D1 (en)
DK (1) DK1280900T3 (en)
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HK (1) HK1111726A1 (en)
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