Compositions and methods for treatment of cancer

Patent metadata

Field	Value
Publication number	US-9464140-B2
Application number	US-201614996953-A
Country	US
Kind code	B2
Filing date	Jan 15, 2016
Priority date	Dec 9, 2010
Publication date	Oct 11, 2016
Grant date	Oct 11, 2016

Abstract

The present invention provides compositions and methods for treating cancer in a human. The invention includes relates to administering a genetically modified T cell to express a CAR wherein the CAR comprises an antigen binding domain, a transmembrane domain, a costimulatory signaling region, and a CD3 zeta signaling domain.

First claim

What is claimed is:

1. A method of treating cancer in a human patient comprising administering to the human patient a pharmaceutical composition comprising an anti-tumor effective amount of a population of human T cells, wherein the T cells comprise a nucleic acid sequence encoding a chimeric antigen receptor (CAR), wherein the CAR comprises a CD19 antigen binding domain comprising, from the amino to the carboxy terminus, a light chain variable region and a heavy chain variable region of SEQ ID NO:20, wherein the CAR further comprises a transmembrane domain, a 4-1BB costimulatory signaling region, and a CD3 zeta signaling domain.

2. The method of claim 1 , wherein the anti-tumor effective amount of the T cells is 10 4 to 10 9 cells per kg body weight of a human in need of such cells.

3. The method of claim 1 , wherein the anti-tumor effective amount of T cells is 10 5 to 10 6 cells per kg body weight of a human in need of such cells.

4. The method of claim 2 , wherein the T cells are administered to the human patient in a single dose divided over three days where 10% of the cells are administered on the first day, 30% of the cells are administered on the second day and 60% of the cells are administered on the third day.

5. The method of claim 4 , further comprising administration of a second dose of the cells to the human patient on the tenth day.

6. The method of claim 1 , wherein the transmembrane domain is CD8α transmembrane domain.

7. The method of claim 6 , wherein the CD8α transmembrane domain comprises the amino acid sequence of SEQ ID NO: 22.

8. The method of claim 1 , wherein the CAR further comprises a hinge domain.

9. The method of claim 8 , wherein the hinge domain is a CD8α hinge domain.

10. The method of claim 9 , wherein the CD8α hinge domain comprises the amino acid sequence of SEQ ID NO:21.

11. The method of claim 1 , wherein the 4-1BB costimulatory signaling region comprises the amino acid sequence of SEQ ID NO:23.

12. The method of claim 1 , wherein the CD3 zeta signaling domain comprises the amino acid sequence of SEQ ID NO: 24.

13. The method of claim 1 , wherein the CD19 antigen binding domain is encoded by a nucleic acid sequence comprising SEQ ID NO: 14.

14. The method of claim 7 , wherein the CD8α transmembrane domain is encoded by a nucleic acid sequence comprising SEQ ID NO: 16.

15. The method of claim 10 , wherein the CD8α hinge domain is encoded by a nucleic acid sequence comprising SEQ ID NO: 15.

16. The method of claim 11 , wherein the 4-1BB costimulatory signaling region is encoded by a nucleic acid sequence comprising SEQ ID NO: 17.

17. The method of claim 12 , wherein the CD3 zeta signaling domain is encoded by a nucleic acid sequence comprising SEQ ID NO: 18.

18. The method of claim 1 , wherein the CAR comprises the amino acid sequence of SEQ ID NO:12.

19. The method of claim 18 , wherein the CAR is encoded by a nucleic acid sequence comprising SEQ ID NO:8.

20. The method of claim 1 , wherein the CAR further comprises a CD28 costimulatory signaling region.

21. The method of claim 1 , wherein the T cells are T cells of a human having a cancer.

22. The method of claim 21 , wherein the cancer is a hematological cancer.

23. The method of claim 1 , wherein the T cells comprise a vector that comprises the nucleic acid sequence.

24. The method of claim 23 , wherein the vector is a lentiviral vector.

25. The method of claim 23 , wherein the vector further comprises a promoter.

26. The method of claim 25 , wherein the promoter is an EF-1α promoter.

27. The method of claim 1 , wherein the pharmaceutical composition further comprises a pharmaceutically acceptable carrier, diluent or excipient.

28. The method of claim 1 , wherein the pharmaceutical composition comprises a buffer.

Assignees

• Univ Pennsylvania

Inventors

• June Carl H
• Levine Bruce L
• Porter David L
• Kalos Michael D
• Milone Michael C

Classifications

• A61P35/00

  Antineoplastic agents · CPC title

• A61P37/04

  Immunostimulants · CPC title

• A61P37/02

  Immunomodulators · CPC title

• A61P35/02

  specific for leukemia · CPC title

• A61P43/00

  Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 · CPC title