Compositions and methods for treatment of cancer

Patent metadata

Field	Value
Publication number	US-9540445-B2
Application number	US-201614997136-A
Country	US
Kind code	B2
Filing date	Jan 15, 2016
Priority date	Dec 9, 2010
Publication date	Jan 10, 2017
Grant date	Jan 10, 2017

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 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, wherein the T cells are from a human having cancer.

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

3. The composition 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 composition of claim 1 , wherein said antigen binding fragment is a scFv.

5. The composition of claim 4 , wherein the scFv comprises the amino acid sequence of SEQ ID NO:20.

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

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

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

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

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

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

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

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

14. The composition of claim 6 , wherein the CD8α transmembrane domain is encoded by a nucleic acid sequence comprising SEQ ID NO: 16.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

29. The composition of claim 28 , wherein the buffer is neutral buffer saline or phosphate buffered saline.

30. The composition of claim 1 , wherein the pharmaceutical composition further comprises a carbohydrate.

Assignees

• Univ Pennsylvania

Inventors

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

Classifications

• A61P35/02

  specific for leukemia · CPC title

• A61P37/02

  Immunomodulators · CPC title

• A61P37/04

  Immunostimulants · CPC title

• A61P35/00

  Antineoplastic agents · CPC title

• A61P43/00

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