METHODS OF ENHANCING T CELL RESPONSIVENESS

• US 20120027759A1
• Filed: 07/13/2010
• Published: 02/02/2012
• Est. Priority Date: 04/20/2001
• Status: Abandoned Application

• Current Assignee: Lieping Chen, Scott E. Strome
• Original Assignee: Lieping Chen, Scott E. Strome
• Inventors: Chen, Lieping, Strome, Scott E.
• Application Number:
  US12/835,410
• Publication Number:
  US 20120027759A1
• Time in Patent Office: Days
• US Class Current: 424/134.1
• CPC Class Codes: A61K 2039/515 Animal cells
• CPC Class Codes: A61K 2239/31 characterized by the route of administration
• CPC Class Codes: A61K 2239/38 characterised by the dose, timing or administration schedule
• CPC Class Codes: A61K 39/4611 T-cells, e.g. tumor infiltrating lymphocytes [TIL], lymphokine-activated killer cells [LAK] or regulatory T cells [Treg]
• CPC Class Codes: A61K 39/4632 T-cell receptors [TCR]; antibody T-cell receptor constructs
• CPC Class Codes: A61K 39/4644 Cancer antigens
• CPC Class Codes: A61K 39/464411 Immunoglobulin superfamily
• CPC Class Codes: A61K 39/464486 MAGE
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 37/04 Immunostimulants
• CPC Class Codes: C07K 16/2827 against B7 molecules, e.g. CD80, CD86
• CPC Class Codes: C07K 2319/00 Fusion polypeptide
• CPC Class Codes: C07K 2319/30 Non-immunoglobulin-derived peptide or protein having an immunoglobulin constant or Fc region, or a fragment thereof, attached thereto
• CPC Class Codes: C12N 2501/23 Interleukins [IL]
• CPC Class Codes: C12N 2501/51 B7 molecules, e.g. CD80, CD86, CD28 (ligand), CD152 (ligand)
• CPC Class Codes: C12N 5/0636 T lymphocytes

Abstract

The invention features methods of enhancing the responsiveness of a T cell. Such methods involve interfering with the interaction between a T cell and a B7-H1 molecule.

Claims

1. A method of enhancing T cell responsiveness in a mammal, the method comprising:

(a) identifying a mammal with, or at risk of developing, cancer, wherein the cells of the cancer are identified as expressing B7-H1 molecules on their surfaces; and

(b) administering to the subject a compound comprising an agent that interferes with an interaction between B7-H1 and a T cell.

2. The method of claim 1, wherein the agent is an antibody that binds to B7-H1.

3. The method of claim 1, wherein the agent is B7-H1 or a functional fragment of B7-H1.

4. The method of claim 1, wherein the agent is a receptor for B7-H1 or a functional fragment of a receptor for B7-H1.

5. The method of claim 3, wherein the compound is a fusion protein.

6. The method of claim 5, wherein the fusion protein further comprises all, or part, of an immunoglobulin constant region.

7. The method of claim 1, wherein the cancer is selected from the group consisting of a hematological cancer, a neurological cancer, melanoma, breast cancer, lung cancer, head and neck cancer, a gastrointestinal cancer, liver cancer, pancreatic cancer, a genitourinary cancer, a bone cancer, and a vascular cancer.

8. The method of claim 1, wherein the mammal is a human.

9. The method of claim 1, further comprising administering an immunogenic stimulus to the mammal.

10. A method of enhancing the responsiveness of a T cell, the method comprising culturing, together, a T cell, a cancer cell identified as expressing B7-H1, and a compound comprising an agent that interferes with an interaction between B7-H1 and a T cell.

11. The method of claim 10, wherein the agent is an antibody that binds to B7-H1.

12. The method of claim 10, wherein the agent is a receptor for B7-H1 or a functional fragment of a receptor for B7-H1.

13. The method of claim 10, wherein the cancer cell is of a cancer selected from the group consisting of a hematological cancer, a neurological cancer, melanoma, breast cancer, lung cancer, head and neck cancer, a gastrointestinal cancer, liver cancer, pancreatic cancer, a genitourinary cancer, a bone cancer, and a vascular cancer.

14. The method of claim 17, wherein the T cell is a CD8+ T cell.

15. The method of claim 17, wherein the T cell is a CD4+ T cell.

16. The method of claim 10, wherein the agent is B7-H1 or a functional fragment of B7-H1.

17. The method of claim 10, wherein the culture further comprises an immunogenic stimulus.