Compositions and methods for treating cancer

Patent metadata

Field	Value
Publication number	US-9402865-B2
Application number	US-201213979927-A
Country	US
Kind code	B2
Filing date	Jan 18, 2012
Priority date	Jan 18, 2011
Publication date	Aug 2, 2016
Grant date	Aug 2, 2016

Abstract

The invention provides compositions and methods for treating ovarian cancer. Specifically, the invention relates to administering a genetically modified T cell having α-folate receptor (FRα) binding domain and 4-1BB (CD137) costimulatory domain to treat ovarian cancer.

First claim

What is claimed is:

1. An isolated nucleic acid sequence encoding a chimeric antigen receptor (CAR), wherein the isolated nucleic acid sequence comprises a nucleic acid sequence encoding an anti-α-folate receptor (FRα) antibody or fragment thereof comprising the amino acid sequence of SEQ ID NO: 23 and a 4-1BB (CD 137) costimulatory domain.

2. The isolated nucleic acid sequence of claim 1 , further comprising a nucleic acid sequence encoding a CD3 zeta signaling domain.

3. The isolated nucleic acid sequence of claim 1 , wherein the CAR comprises an amino acid sequence of SEQ ID NO: 22.

4. The isolated nucleic acid sequence of claim 1 comprising a nucleic acid sequence of SEQ ID NO: 20.

5. The isolated nucleic acid sequence of claim 1 , wherein the anti-FRα antibody or fragment thereof binds to a tumor antigen, wherein the tumor antigen is FRα.

6. The isolated nucleic acid sequence of claim 5 , wherein the tumor antigen is associated with an epithelial malignancy.

7. The isolated nucleic acid sequence of claim 5 , wherein the tumor antigen is associated with a solid tumor.

8. The isolated nucleic sequence of claim 1 , wherein the 4-1BB costimulatory domain comprises an amino acid sequence of SEQ ID NO: 18.

9. The isolated nucleic acid sequence of claim 1 , wherein the 4-1BB costimulatory domain is encoded by the nucleic acid sequence of SEQ ID NO: 6.

10. The isolated nucleic sequence of claim 2 , wherein the CD3 zeta signaling domain comprises an amino acid sequence of SEQ ID NO: 19.

11. The isolated nucleic acid sequence of claim 2 , wherein the CD3 zeta signaling domain is encoded by a nucleic acid sequence of SEQ ID NO: 7.

12. The isolated nucleic acid sequence of claim 1 , further comprising the nucleic acid sequence of a transmembrane domain.

13. An isolated chimeric antigen receptor (CAR), wherein the CAR comprises an anti-α-folate receptor (FRα) antibody or fragment thereof comprising the amino acid sequence of SEQ ID NO: 23 and a 4-1BB (CD 137) costimulatory domain.

14. The isolated CAR of claim 13 further comprising a CD3 zeta signaling domain.

15. The isolated CAR of claim 13 , wherein the CAR comprises the amino acid sequence of SEQ ID NO: 22.

16. The isolated CAR of claim 13 , wherein the FRα binding domain binds to a tumor antigen, wherein the tumor antigen is FRα.

17. The isolated CAR of claim 16 , wherein the tumor antigen is associated with an epithelial malignancy.

18. The isolated CAR of claim 16 , wherein the tumor antigen is associated with a solid tumor.

19. The isolated CAR of claim 13 , wherein the 4-1BB costimulatory domain comprises the amino acid sequence of SEQ ID NO: 18.

20. The isolated CAR of claim 14 , wherein the CD3 zeta signaling domain comprises the amino acid sequence of SEQ ID NO: 19.

21. The isolated CAR of claim 13 , further comprising a transmembrane domain.

22. A genetically modified T cell comprising the isolated nucleic acid sequence of claim 1 .

23. A vector comprising the isolated nucleic acid sequence of claim 1 .

24. A method for providing an anti-tumor immunity in a subject, the method comprising: administering to the subject an effective amount of the genetically modified T cell of claim 22 , thereby providing anti-tumor immunity in a subject.

25. The method of claim 24 , wherein the isolated nucleic acid sequence further comprises the nucleic acid sequence of a CD3 zeta signaling domain.

26. The method of claim 24 , wherein the presence of the costimulatory domain enhances T cell survival.

27. The method of claim 24 , wherein the presence of the costimulatory domain increases the efficacy of anti-tumor immunity in a subject.

28. The method of claim 24 , wherein the subject is a mammal.

29. The method of claim 24 , wherein the subject is a human.

30. A method for stimulating a T-cell mediated immune response to a cell population or tissue in a subject, the method comprising: administering to the subject an effective amount of the genetically modified T cell of claim 22 , thereby stimulating a T-cell mediated immune response in the subject.

31. A method for treating an ovarian cancer in a subject, the method comprising: administering to the subject an effective amount of the genetically modified T cell of claim 22 , thereby treating the ovarian cancer in the subject.

32. A method for treating an cancer in a subject, the method comprising: administering to the subject an effective amount of the genetically modified T cell of claim 22 , thereby treating the cancer in the subject.

33. A method for generating a persisting population of genetically engineered T cells in a subject diagnosed with ovarian cancer, the method comprising: administering to the subject an effective amount of the genetically modified T cell of claim 22 , wherein the persisting population of genetically engineered T cells persists in the subject for at least one month after administration.

34. The method of claim 33 , wherein the persisting population of genetically engineered T cells persists in the human for at least three months after administration.

Assignees

• Powell Daniel J
• Coukos George
• Univ Pennsylvania

Inventors

• Powell Daniel J
• Coukos George

Classifications

• A61P35/00

  Antineoplastic agents · CPC title

• A61P37/04

  Immunostimulants · CPC title

• C07K14/70517

  CD8 · CPC title

• C07K2317/622

  Single chain antibody (scFv) · CPC title

• A61K39/39558

  against tumor tissues, cells, antigens · CPC title