Bi-spcific chimeric T cells

• US 20030148982A1
• Filed: 11/08/2002
• Published: 08/07/2003
• Est. Priority Date: 11/13/2001
• Status: Abandoned Application

• Current Assignee: Baylor College of Medicine (Baylor College)
• Original Assignee: Baylor College of Medicine (Baylor College)
• Inventors: Rossig, Claudia, Rooney, Cliona, Brenner, Malcolm K.
• Application Number:
  US10/290,720
• Publication Number:
  US 20030148982A1
• Time in Patent Office: Days
• US Class Current: 514/44
• CPC Class Codes: A61K 2039/505 comprising antibodies
• CPC Class Codes: A61K 2239/29 Multispecific CARs
• 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 39/4631 Chimeric Antigen Receptors [CAR]
• CPC Class Codes: A61K 39/4632 T-cell receptors [TCR]; antibody T-cell receptor constructs
• CPC Class Codes: A61K 39/464412 CD19 or B4
• CPC Class Codes: A61K 39/464471 Gangliosides, e.g. GM2, GD2 or GD3
• CPC Class Codes: A61K 39/464838 Viral antigens
• CPC Class Codes: C07K 16/2803 against the immunoglobulin superfamily
• CPC Class Codes: C07K 2317/622 Single chain antibody (scFv)
• CPC Class Codes: C07K 2319/00 Fusion polypeptide
• CPC Class Codes: C12N 2799/027 where the vector is derived from a retrovirus

Abstract

The present invention is directed to a bi-specific chimeric T lymphocyte, wherein the lymphocyte comprises both an antigen-specific receptor, such as for Epstein-Barr Virus, and a chimeric receptor, such as for a tumor. In a particular embodiment, administration of an Epstein-Barr Virus T lymphocyte with an 14.G2a-ζ antitumor chimeric receptor is utilized for therapy of neuroblastoma.

Claims

1. A T lymphocyte, comprising:

an antigen-specific receptor, wherein the presence of said antigen-specific receptor leads to increased in vivo survival of said lymphocyte; and

a chimeric receptor.

2. The lymphocyte of claim 1, wherein the antigen for said antigen-specific receptor comprises a viral polypeptide.

3. The lymphocyte of claim 2, wherein said viral polypeptide is an Epstein Barr Virus polypeptide.

4. The lymphocyte of claim 1, wherein said chimeric receptor further comprises an antigen-binding moiety.

5. The lymphocyte of claim 4, wherein said antigen-binding moiety is a single chain antibody.

6. The lymphocyte of claim 1, wherein said chimeric receptor is an antitumor chimeric receptor.

7. The lymphocyte of claim 1, wherein said antitumor chimeric receptor is 14.G2a-ζ

.

8. The lymphocyte of claim 6, wherein said antitumor chimeric receptor is CD19 specific.

9. A cytotoxic T lymphocyte, comprising:

an Epstein Barr Virus-specific receptor, wherein the presence of said receptor leads to increased in vivo survival of said lymphocyte; and

a 14.G2a-ζ

chimeric receptor.

10. A cytotoxic T lymphocyte, comprising:

an Epstein Barr Virus-specific receptor, wherein the presence of said receptor leads to increased in vivo survival of said lymphocyte; and

a CD 19 specific chimeric receptor.

11. A population of cytotoxic T lymphocytes, comprising at least one cytotoxic T lymphocyte having:

an antigen-specific receptor, wherein the presence of said antigen-specific receptor leads to increased in vivo survival of said lymphocyte; and

a chimeric receptor.

12. The population of lymphocytes of claim 11, wherein the population comprises CD4⁺ T lymphocytes, CD8⁺ T lymphocytes, or a combination thereof.

13. The population of claim 11, wherein the antigen for said antigen-specific receptor comprises a viral polypeptide.

14. The population of claim 11, wherein said viral polypeptide is an Epstein Barr Virus polypeptide.

15. The population of claim 11, wherein said chimeric receptor is an antitumor chimeric receptor.

16. The population of claim 15, wherein said antitumor chimeric receptor is 14.G2a-ζ

.

17. The population of claim 15, wherein said antitumor chimeric receptor is CD19 specific.

18. A method of enhancing activity of a chimeric T lymphocyte in an individual, comprising:

obtaining a T lymphocyte, wherein said T lymphocyte comprises

an antigen-specific receptor, wherein the presence of said antigen-specific receptor leads to increased in vivo survival of said lymphocyte; and

a chimeric receptor; and

administering said cell to said individual.

19. The method of claim 18, wherein said antigen is an Epstein-Barr Virus polypeptide.

24. The method of claim 18, 20, or 22, wherein said obtaining step is further defined as:

transfecting into a T lymphocyte a vector comprising a polynucleotide encoding said chimeric receptor.

25. The method of claim 24, wherein said vector is a retroviral vector.

20. A method of treating a disease in an individual, wherein said disease is associated with a pathogen or cell having a first antigen, comprising:

obtaining a cytotoxic T lymphocyte, wherein said lymphocyte comprises;

a receptor specific for a second antigen, wherein the presence of said second antigen-specific receptor leads to increased in vivo survival of said lymphocyte; and

a chimeric receptor specific for said first antigen; and

administering said T lymphocyte to said individual.

21. The method of claim 20, wherein said disease is cancer and said first antigen is a tumor-specific or tumor-associated antigen.

23. The method of claim 20 or 22, wherein said antigen is an Epstein-Barr Virus polypeptide.

22. A method of treating a tumor in an individual, comprising:

obtaining a cytotoxic T lymphocyte, wherein said lymphocyte comprises;

an antigen-specific receptor, wherein the presence of said antigen-specific receptor leads to increased in vivo survival of said lymphocyte; and

an antitumor chimeric receptor; and

administering said T lymphocyte to said individual.

26. The method of claim 22, wherein said antitumor chimeric receptor is 14.G2a-ζ

.

27. The method of claim 22, wherein said antitumor chimeric receptor is CD-19 specific.

28. The method of claim 22, wherein the tumor is of neural crest origin.

29. The method of claim 28, wherein the tumor of neural crest origin is neuroblastoma or ganglioneuroma.

30. The method of claim 22, wherein the tumor is from lung cancer, melanoma, breast cancer, prostate cancer, colon cancer, or lymphoma.

31. The method of claim 30, wherein the lymphoma is of B cell origin.

32. The method of claim 22, further comprising administering to said individual an additional cancer therapy.

33. The method of claim 32, wherein said additional cancer therapy is chemotherapy, radiation, surgery, or a combination thereof.

34. A method of preventing cancer or an intractable infection in an individual, wherein said cancer or intractable infection is associated with a pathogen or cell having a first antigen, comprising administering to an individual susceptible to said cancer or intractable infection at least one cytotoxic T lymphocyte, wherein the lymphocyte comprises:

a receptor specific for a second antigen, wherein the presence of said second antigen-specific receptor leads to increased in vivo survival of said lymphocyte; and

a chimeric receptor specific for said first antigen.

35. The method of claim 34, wherein said second antigen is an Epstein-Barr Virus polypeptide.

36. The method of claim 34, wherein said cancer is of neural crest origin.

37. The method of claim 34, wherein said cancer is lung cancer, melanoma, breast cancer, prostate cancer, colon cancer, or lymphoma.

38. The method of claim 37, wherein the lymphoma is of B cell origin.

39. The method of claim 34, wherein said intractable infection is a viral infection or a bacterial infection.

40. The method of claim 38, wherein said viral infection is acquired immunodeficiency syndrome (AIDS), hepatitis B or hepatitis C.

41. A kit, housed in a suitable container, comprising:

at least one cytotoxic T lymphocyte in a pharmaceutically acceptable solution, comprising;

a chimeric receptor specific for said first antigen; and

a receptor specific for a second antigen, wherein the presence of said second antigen-specific receptor leads to increased in vivo survival of said lymphocyte.

42. The kit of claim 41, wherein said second antigen is an Epstein-Barr Virus polypeptide.