Methods for treatment of cancer
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.
1. A method of treating a hematological cancer in a human patient, the method comprising administering to the human patient a pharmaceutical composition comprising an antitumor effective amount of a population of human T cells, wherein the cells of the population include cells that comprise a nucleic acid sequence that encodes a chimeric antigen receptor (CAR), wherein the CAR comprises a CD19 antigen binding domain comprising the amino acid sequence of SEQ ID NO: 20, a CD8α hinge domain, a CD8α transmembrane domain, a 4-1BB costimulatory signaling region, and a CD3 zeta signaling domain, wherein the T cells are T cells of a human patient having a hematological cancer.
2. The method of claim 1 , wherein the anti-tumor effective amount of T cells is 10 4 to 10 9 cells per kg body weight of the human patient.
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 the human patient.
4. The method of claim 1 , wherein the CD8α transmembrane domain comprises the amino acid sequence of SEQ ID NO: 22.
5. The method of claim 1 , wherein the CD8α hinge domain comprises the amino acid sequence of SEQ ID NO: 21.
6. The method of claim 1 , wherein the 4-1BB costimulatory signaling region comprises the amino acid sequence of SEQ ID NO: 23.
7. The method of claim 1 , wherein the CD3 zeta signaling domain comprises the amino acid sequence of SEQ ID NO: 24.
8. The method of claim 1 , wherein the CD19 binding domain is encoded by a nucleic acid sequence comprising SEQ ID NO: 14.
9. The method of claim 4 , wherein the CD8α transmembrane domain is encoded by a nucleic acid sequence comprising SEQ ID NO: 16.
10. The method of claim 5 , wherein the CD8α hinge domain is encoded by a nucleic acid sequence comprising SEQ ID NO: 15.
11. The method of claim 6 , wherein the 4-1BB costimulatory signaling region is encoded by a nucleic acid sequence comprising SEQ ID NO: 17.
12. The method of claim 7 , wherein the CD3 zeta signaling domain is encoded by a nucleic acid sequence comprising SEQ ID NO: 18.
13. The method of claim 1 , wherein the hematological cancer is leukemia.
14. The method of claim 13 , wherein the leukemia is chronic lymphocytic leukemia (CLL) or acute lymphocytic leukemia (ALL).
15. The method of claim 1 , wherein the hematological cancer is lymphoma.
16. The method of claim 15 , wherein the lymphoma is non-Hodgkin's lymphoma, Hodgkin's lymphoma or mantle cell lymphoma.
17. The method of claim 1 , wherein the hematological cancer is multiple myeloma.
18. The method of claim 4 , wherein the CD8α hinge domain comprises the amino acid sequence of SEQ ID NO: 21.
19. The method of claim 18 , wherein the CD8α hinge domain is encoded by a nucleic acid sequence comprising SEQ ID NO: 15.
20. The method of claim 6 , wherein the CD8α hinge domain comprises the amino acid sequence of SEQ ID NO: 21.
21. The method of claim 20 , wherein the CD8α hinge domain is encoded by a nucleic acid sequence comprising SEQ ID NO: 15.
22. The method of claim 7 , wherein the CD8α hinge domain comprises the amino acid sequence of SEQ ID NO: 21.
23. The method of claim 22 , wherein the CD8α hinge domain is encoded by a nucleic acid sequence comprising SEQ ID NO: 15.
24. The method of claim 6 , wherein the CD8α transmembrane domain comprises the amino acid sequence of SEQ ID NO: 22.
25. The method of claim 24 , wherein the CD8α transmembrane domain is encoded by a nucleic acid sequence comprising SEQ ID NO: 16.
26. The method of claim 7 , wherein the CD8α transmembrane domain comprises the amino acid sequence of SEQ ID NO: 22.
27. The method of claim 26 , wherein the CD8α transmembrane domain is encoded by a nucleic acid sequence comprising SEQ ID NO: 16.
28. A method of treating lymphoma in a human patient, the method comprising administering to the human patient a pharmaceutical composition comprising an antitumor effective amount of a population of human T cells, wherein the cells of the population include cells that comprise a nucleic acid sequence that encodes a chimeric antigen receptor (CAR), wherein the CAR comprises a CD19 antigen binding domain comprising the amino acid sequence of SEQ ID NO:20, a CD8α hinge domain comprising the amino acid sequence of SEQ ID NO:21, a CD8α transmembrane domain comprising the amino acid sequence of SEQ ID NO:22, a 4-1 BB costimulatory signaling region comprising the amino acid sequence of SEQ ID NO:23, and a CD3 zeta signaling domain comprising the amino acid sequence of SEQ ID NO:24, wherein the T cells are T cells of a human patient having lymphoma.
29. The method of claim 28 , wherein the lymphoma is non-Hodgkin's lymphoma, Hodgkin's lymphoma or mantle cell lymphoma.
30. A method of treating multiple myeloma in a human patient, the method comprising administering to the human patient a pharmaceutical composition comprising an antitumor effective amount of a population of human T cells, wherein the cells of the population include cells that comprise a nucleic acid sequence that encodes a chimeric antigen receptor (CAR), wherein the CAR comprises a CD19 antigen binding domain comprising the amino acid sequence of SEQ ID NO:20, a CD8α hinge domain comprising the amino acid sequence of SEQ ID NO:21, a CD8α transmembrane domain comprising the amino acid sequence of SEQ ID NO:22, a 4-1 BB costimulatory signaling region comprising the amino acid sequence of SEQ ID NO:23, and a CD3 zeta signaling domain comprising the amino acid sequence of SEQ ID NO:24, wherein the T cells are T cells of a human patient having multiple myeloma.