Methods of using B7-DC molecules to induce or enhance an immune response
First Claim
1. A method for increasing the immune response of a mammalian subject to antigenic stimulation comprising administering an effective amount of a fusion protein to increase T cell proliferation relative to a control, wherein the fusion protein comprises a first fusion partner comprising all or a part of a B7-DC protein comprising an extracellular domain which(i) is fused to a second polypeptide or(ii) is fused to a linker peptide sequence that is fused to the second polypeptidewherein the B7-DC protein has at least 70% sequence identity to SEQ ID NO:
- 2.
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Accused Products
Abstract
A novel costimulatory protein molecule, B7-DC, which is a member of the B7 family, is described as is DNA coding therefor and expression vectors comprising this 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-tumor and anti-viral immunity.
107 Citations
45 Claims
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1. A method for increasing the immune response of a mammalian subject to antigenic stimulation comprising administering an effective amount of a fusion protein to increase T cell proliferation relative to a control, wherein the fusion protein comprises a first fusion partner comprising all or a part of a B7-DC protein comprising an extracellular domain which
(i) is fused to a second polypeptide or (ii) is fused to a linker peptide sequence that is fused to the second polypeptide wherein the B7-DC protein has at least 70% sequence identity to SEQ ID NO:
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2. A method for inducing or enhancing an immune response to an antigen in a mammalian subject comprising administering to the subject:
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(a) an effective amount of a vaccine composition comprising a fusion protein comprising a first fusion partner comprising all or a part of a B7-DC protein comprising an extracellular domain which (i) is fused to a second polypeptide or (ii) is fused to a linker peptide sequence that is fused to the second polypeptide, wherein the B7-DC protein has at least 70% sequence identity to SEQ ID NO;
2; and(b) a source of the antigen. - View Dependent Claims (29, 31)
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3. A method for potentiating an immune response to an antigen or a vaccine in a mammalian subject, comprising administering to the subject, in combination with the antigen or vaccine, a fusion protein comprising a first fusion partner comprising all or a part of a B7-DC protein comprising an extracellular domain which
(i) is fused to a second polypeptide or (ii) is fused to a linker peptide sequence that is fused to the second polypeptide, wherein the B7-DC protein has at least 70% sequence identity to SEQ ID NO: - 2.
- 13. A method for increasing the immune response of a mammalian subject to antigenic stimulation comprising administering an effective amount of a fusion polypeptide of the extracellular domain of murine or human B7-DC, wherein the B7-DC polypeptide is selectively expressed on dendritic cells as compared to activated macrophages, wherein murine B7-DC polypeptide has 32% homology to human B7-H1, wherein the B7-DC polypeptide comprises single IgV and IgC domains, wherein the B7-DC polypeptide comprises a single transmembrane domain, wherein the murine B7-DC polypeptide comprises an intracytoplasmic tail 4 amino acids in length, wherein the B7-DC polypeptide does not bind to CD28 or CTLA-4 and does not include the CD28/CTLA-4 binding motifs, and wherein the B7-DC polypeptide is capable of co-stimulating T cells.
- 18. A method for increasing the immune response of a mammalian subject to antigenic stimulation comprising administering an effective amount of a mature polypeptide comprising a first fusion partner and a second fusion partner, wherein the first fusion partner consists of the extracellular domain of B7-DC.
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21. A method for increasing an immune response in a human comprising administering to the human an effective amount of a fusion protein,
wherein the fusion protein comprises a first fusion partner consisting of amino acids 20-221 of SEQ ID NO: - 2 and a second fusion partner consisting of the hinge, CH2 and CH3 regions of a human immunoglobulin Cγ
1 chain,wherein the human has melanoma.
- 2 and a second fusion partner consisting of the hinge, CH2 and CH3 regions of a human immunoglobulin Cγ
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22. A method for increasing an immune response in a human comprising administering to the human an effective amount of a fusion protein,
wherein the fusion protein comprises a first fusion partner consisting of amino acids 20-221 of SEQ ID NO: - 2 and a second fusion partner consisting of the hinge, CH2 and CH3 regions of a human immunoglobulin Cγ
1 chain,wherein the human has carcinoma. - View Dependent Claims (23, 24, 25, 26, 27, 28)
- 2 and a second fusion partner consisting of the hinge, CH2 and CH3 regions of a human immunoglobulin Cγ
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32. A method for increasing an immune response in a human comprising administering to the human an effective amount of a fusion protein,
wherein the fusion protein comprises a first fusion partner consisting of amino acids 20-221 of SEQ ID NO: - 2 and a second fusion partner consisting of the hinge, CH2 and CH3 regions of a human immunoglobulin Cγ
1 chain,wherein the human has a viral infection. - View Dependent Claims (33, 34)
- 2 and a second fusion partner consisting of the hinge, CH2 and CH3 regions of a human immunoglobulin Cγ
Specification