MART-1 T CELL RECEPTORS

• US 20080199424A1
• Filed: 09/28/2007
• Published: 08/21/2008
• Est. Priority Date: 09/29/2006
• Status: Active Grant

• Current Assignee: California Institute of Technology, Regents of the University of California (University of California)
• Original Assignee: Regents of the University of California (University of California)
• Inventors: Baltimore, David, Yang, Lili, Wang, Pin, Ribas, Antoni, Economou, James
• Granted Patent: US 8,119,772 B2
• Time in Patent Office: Days
• US Class Current: 424/85.2
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: C07K 14/4748 Tumour specific antigens; Tumour rejection antigen precursors [TRAP], e.g. MAGE

Abstract

T-cell receptors that recognize MART-1 antigen are provided. The TCRs can be used, for example, to treat patients suffering from melanoma.

Claims

1. An isolated nucleic acid encoding a TCR-α

subunit polypeptide comprising an amino acid sequence having at least 80% sequence identity to SEQ ID NO;

3.

2. An isolated nucleic acid encoding a polypeptide comprising a TCR-α

variable region comprising an amino acid sequence having at least 80% sequence identity to SEQ ID NO;

4.

3. An isolated nucleic acid encoding a TCR-β

subunit polypeptide comprising an amino acid sequence having at least 95% sequence identity to SEQ ID NO;

7.

4. An isolated nucleic acid encoding a polypeptide comprising a TCR-β

variable region comprising an amino acid sequence having at least 95% sequence identity to SEQ ID NO;

8.

5. An isolated nucleic acid encoding a TCR-β

subunit polypeptide comprising an amino acid sequence having at least 80% sequence identity to SEQ ID NO;

15.

6. An isolated nucleic acid encoding a polypeptide comprising a TCR-β

variable region comprising an amino acid sequence having at least 80% sequence identity to SEQ ID NO;

16.

7. An isolated polypeptide comprising an amino acid sequence with at least 80% sequence identity to SEQ ID NO:

3.

8. An isolated polypeptide comprising an amino acid sequence with at least 80% sequence identity to SEQ ID NO:

4.

9. An isolated polypeptide comprising an amino acid sequence with at least 95% sequence identity to SEQ ID NO:

7.

10. An isolated polypeptide comprising an amino acid sequence with at least 95% sequence identity to SEQ ID NO:

8.

11. An isolated polypeptide comprising an amino acid sequence with at least 80% sequence identity to SEQ ID NO:

15.

12. An isolated polypeptide comprising an amino acid sequence with at least 80% sequence identity to SEQ ID NO:

16.

13. A cell containing a TCR comprising a polypeptide having at least 80% sequence identity to SEQ ID NO:

4.

14. The cell of claim 13, wherein the TCR further comprises a polypeptide having at least 80% sequence identity to SEQ ID NO:

8.

19. The vector of claim 14, further comprising a nucleic acid having at least 80% sequence identity to SEQ ID NO:

6.

15. A cell containing a TCR comprising a polypeptide having at least 95% sequence identity to SEQ ID NO:

8.

16. A cell containing a TCR comprising a polypeptide having at least 80% sequence identity to SEQ ID NO:

16.

17. The cell of claim 16, wherein the TCR further comprises a polypeptide having at least 80% sequence identity to SEQ ID NO:

12.

18. A vector comprising a nucleic acid having at least 80% sequence identity to SEQ ID NO:

2.

20. A vector comprising a nucleic acid having at least 95% sequence identity to SEQ ID NO:

6.

21. A vector comprising a nucleic acid having at least 80% sequence identity to SEQ ID NO:

14.

22. The vector of claim 21, further comprising a nucleic acid having at least 80% sequence identity to SEQ ID NO:

10.

23. A recombinant virus comprising at least one of:

a nucleic acid having at least 80% sequence identity to SEQ ID NO;

2;

a nucleic acid having at least 95% sequence identity to SEQ ID NO;

6; and

an isolated nucleic acid having at least 80% sequence identity to SEQ ID;

14.

24. The recombinant virus of claim 23, further comprising a suicide gene.

25. The recombinant virus of claim 24, wherein the suicide gene is sr39tk gene having a sequence comprising SEQ ID NO:

18.

26. A method of treating melanoma in a patient in need of treatment, comprising:

providing a population of target cells;

transducing the population of target cells by contacting the target cells with a virus comprising at least one of;

a nucleic acid having at least 80% sequence identity to SEQ ID NO;

2, a nucleic acid having at least 95% sequence identity to SEQ ID NO;

6 and a nucleic acid having at least 80% sequence identity to SEQ ID;

14; and

administering the population of transduced target cells to the patient.

27. The method of claim 26, wherein the target cells are peripheral blood mononuclear cells (PMBCs).

28. The method of claim 27, further comprising contacting the target cells with at least one of the following:

CD2, CD3, and CD28.

29. The method of claim 28, further comprising isolating CD8+ T cells from the population of target cells.

30. The method of claim 26, wherein the target cells are hematopoietic stem cells (HSCs).

31. The method of claim 26, wherein the transduced target cells express a T-cell receptor that specifically recognizes MART-1.

32. The method of claim 26, further comprising mixing the transduced target cell population with unmanipulated cells, wherein the population of transduced target cells is administered as the mixture to the patient.

33. The method of claim 26, further comprising administering at least one dose of interleukin-2 (IL-2) to the patient.

34. The method of claim 26, further comprising administering a MART-1 dendritic cell vaccine to the patient.

35. A method of treating melanoma in a patient in need of treatment, comprising:

providing a population of target cells;

transducing the population of target cells by contacting the target cells with a virus comprising a nucleic acid having at least 80% sequence identity to SEQ ID NO;

2 and a nucleic acid having at least 80% sequence identity to SEQ ID NO;

6; and

administering the population of transduced target cells to the patient.

36. A method of treating melanoma in a patient in need of treatment, comprising:

providing a population of target cells;

transducing the population of target cells by contacting the target cells with a virus comprising a nucleic acid having at least 80% sequence identity to SEQ ID NO;

and a nucleic acid having at least 80% sequence identity to SEQ ID NO;

14; and

administering the population of transduced target cells to the patient.

37. A method of generating T cells against MART-1 antigen, comprising:

providing a population of cells comprising T cells; and

contacting the population of cells with a recombinant virus comprising at least one of;

a nucleic acid having at least 80% sequence identity to SEQ ID NO;

2, a nucleic acid having at least 95% sequence identity to SEQ ID NO;

6 and an isolated nucleic acid having at least 80% sequence identity to SEQ ID;

14.

38. The method of claim 37, further comprising contacting the population of cells with at least one of the following:

CD2, CD3, and CD28.

39. The method of claim 37, further comprising isolating CD8+ T cells from the population of cells.

40. A method of generating T cells against MART-1 antigen, comprising:

providing a population of cells comprising T cells; and

contacting the population of cells with a recombinant virus comprising a nucleic acid having at least 80% sequence identity to SEQ ID NO;

2 and a nucleic acid having at least 80% sequence identity to SEQ ID NO;

6.

41. A method of generating T cells against MART-1 antigen, comprising:

providing a population of cells comprising T cells; and

contacting the population of cells with a recombinant virus comprising a nucleic acid having at least 80% sequence identity to SEQ ID NO;

10 and a nucleic acid having at least 80% sequence identity to SEQ ID NO;

14.

42. A method of generating an immune response against MART-1 antigen in a patient, comprising:

providing a population of target cells;

transducing the population of target cells by contacting the target cells with a virus comprising at least one of;

a nucleic acid having at least 80% sequence identity to SEQ ID NO;

2, a nucleic acid having at least 95% sequence identity to SEQ ID NO;

6 and a nucleic acid having at least 80% sequence identity to SEQ ID;

14; and

administering the population of transduced target cells to the patient.

43. A method of generating an immune response against MART-1 antigen in a patient, comprising:

providing a population of target cells;

transducing the population of target cells by contacting the target cells with a virus comprising a nucleic acid having at least 80% sequence identity to SEQ ID NO;

2 and a nucleic acid having at least 80% sequence identity to SEQ ID NO;

6; and

administering the population of transduced target cells to the patient.

44. A method of generating an immune response against MART-1 antigen in a patient, comprising:

providing a population of target cells;

transducing the population of target cells by contacting the target cells with a virus comprising a nucleic acid having at least 80% sequence identity to SEQ ID NO;

and a nucleic acid having at least 80% sequence identity to SEQ ID NO;

14; and

administering the population of transduced target cells to the patient.