Compositions and methods for treating cancer

Patent metadata

Field	Value
Publication number	US-10457729-B2
Application number	US-201615212916-A
Country	US
Kind code	B2
Filing date	Jul 18, 2016
Priority date	Jan 18, 2011
Publication date	Oct 29, 2019
Grant date	Oct 29, 2019

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 α-folate receptor (FRα) antibody comprising the amino acid sequence of SEQ ID NO: 23.

2. The isolated nucleic acid sequence of claim 1 , wherein the CAR further comprises a CD3 zeta signaling domain.

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

4. 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.

5. The isolated nucleic acid sequence of claim 1 , wherein the CAR further comprises a transmembrane domain.

6. An isolated chimeric antigen receptor (CAR), wherein the CAR comprises an anti-folate receptor (FRα) antibody comprising the amino acid sequence of SEQ ID NO: 23.

7. The isolated CAR of claim 6 , wherein the CAR further comprises a CD3 zeta signaling domain.

8. The isolated CAR of claim 7 , wherein the CD3 zeta signaling domain comprises an amino acid sequence of SEQ ID NO: 19.

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

10. The isolated CAR of claim 6 , wherein the CAR further comprises a transmembrane domain.

11. A method for providing anti-tumor immunity in a subject, the method comprising:
administering to the subject an effective amount of a T cell comprising the CAR of claim 6 , thereby providing anti-tumor immunity in the subject.

12. The method of claim 11 , wherein the CAR further comprises a 4-1BB costimulatory domain.

13. The method of claim 12 , wherein the 4-1BB costimulatory domain comprises an amino acid sequence of SEQ ID NO: 18.

14. The method of claim 12 , wherein the 4-1BB costimulatory domain is encoded by the nucleic acid sequence of SEQ ID NO: 6.

15. 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 a T cell comprising the CAR of claim 6 , thereby stimulating a T cell-mediated immune response in the subject.

16. The method of claim 15 , wherein the CAR further comprises a 4-1BB costimulatory domain.

17. The method of claim 16 , wherein the 4-1BB costimulatory domain comprises an amino acid sequence of SEQ ID NO: 18.

18. The method of claim 16 , wherein the 4-1BB costimulatory domain is encoded by the nucleic acid sequence of SEQ ID NO: 6.

19. A method for treating an ovarian cancer in a subject, the method comprising:
administering to the subject an effective amount of a T cell comprising the CAR of claim 6 , thereby treating the ovarian cancer in the subject.

20. The method of claim 19 , wherein the CAR further comprises a 4-1BB costimulatory domain.

21. The method of claim 20 , wherein the 4-1BB costimulatory domain comprises an amino acid sequence of SEQ ID NO: 18.

22. The method of claim 20 , wherein the 4-1BB costimulatory domain is encoded by the nucleic acid sequence of SEQ ID NO: 6.

23. A method for treating cancer in a subject, the method comprising: administering to the subject an effective amount of a T cell comprising the CAR of claim 6 , thereby treating cancer in the subject.

24. The method of claim 23 , wherein the CAR further comprises a 4-1BB costimulatory domain.

25. The method of claim 24 , wherein the 4-1BB costimulatory domain comprises an amino acid sequence of SEQ ID NO: 18.

26. The method of claim 24 , wherein the 4-1BB costimulatory domain is encoded by the nucleic acid sequence of SEQ ID NO: 6.

27. A method of 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 a T cell comprising the CAR of claim 6 , wherein the persisting population of genetically engineered T cells persists in the subject for at least one month after administration.

28. The method of claim 27 , wherein the CAR further comprises a 4-1BB costimulatory domain.

29. The method of claim 28 , wherein the 4-1BB costimulatory domain comprises an amino acid sequence of SEQ ID NO: 18.

30. The method of claim 28 , wherein the 4-1BB costimulatory domain is encoded by the nucleic acid sequence of SEQ ID NO: 6.

Assignees

• Univ Pennsylvania
• Fondazione Irccs Istituto Naz Dei Tumori

Inventors

• Powell Daniel J
• Coukos George
• Figini Mariangela
• Canevari Silvana

Classifications

• A61P37/04

  Immunostimulants · CPC title

• A61P35/00

  Antineoplastic agents · CPC title

• C07K2319/74

  containing a fusion for binding to a cell surface receptor · CPC title

• C07K14/7051

  T-cell receptor (TcR)-CD3 complex · CPC title

• A61K39/39558

  against tumor tissues, cells, antigens · CPC title