Compositions and methods for treatment of cancer

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.