Compositions 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 pharmaceutical composition comprising an anti-tumor effective amount of a population of human T cells, wherein the T cells 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 comprising the amino acid sequence of SEQ ID NO:24, wherein the T cells are T cells of a human having a 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 CD8α transmembrane domain comprises the amino acid sequence of SEQ ID NO: 22.
4. The composition of claim 1 , wherein the CD8α hinge domain comprises the amino acid sequence of SEQ ID NO: 21.
5. The composition of claim 1 , wherein the 4-1BB costimulatory signaling region comprises the amino acid sequence of SEQ ID NO: 23.
6. The composition of claim 1 , wherein the CD19 antigen binding domain is encoded by a nucleic acid sequence comprising SEQ ID NO: 14.
7. The composition of claim 3 , wherein the CD8α transmembrane domain is encoded by a nucleic acid sequence comprising SEQ ID NO: 16.
8. The composition of claim 4 , wherein the CD8α hinge domain is encoded by a nucleic acid sequence comprising SEQ ID NO: 15.
9. The composition of claim 5 , wherein the 4-1BB costimulatory signaling region is encoded by a nucleic acid sequence comprising SEQ ID NO: 17.
10. The composition of claim 1 , wherein the CD3 zeta signaling domain is encoded by a nucleic acid sequence comprising SEQ ID NO: 18.
11. The composition of claim 3 , wherein the 4-1BB costimulatory signaling region comprises the amino acid sequence of SEQ ID NO:23.
12. The composition of claim 11 , wherein the 4-1BB costimulatory signaling region of the CAR is encoded by a nucleic acid sequence comprising SEQ ID NO:17.
13. The composition of claim 4 , wherein the 4-1BB costimulatory signaling region comprises the amino acid sequence of SEQ ID NO:23.
14. The composition of claim 13 , wherein the 4-1BB costimulatory signaling region is encoded by a nucleic acid sequence comprising SEQ ID NO:17.
15. 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 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 4-1BB 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 having a cancer.
16. The composition of claim 15 , wherein the CD19 antigen binding domain of the CAR is encoded by a nucleic acid sequence comprising SEQ ID NO:14, the CD8α hinge domain of the CAR is encoded by a nucleic acid sequence comprising SEQ ID NO:15, the CD8α transmembrane domain of the CAR is encoded by a nucleic acid sequence comprising SEQ ID NO:16, the 4-1BB costimulatory signaling region of the CAR is encoded by a nucleic acid sequence comprising SEQ ID NO:17, and the CD3 zeta signaling domain of the CAR is encoded by a nucleic acid sequence comprising SEQ ID NO:18.
17. The composition of claim 15 , 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.
18. The composition of claim 15 , 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.
19. 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.
20. The composition of claim 3 , wherein the CD8α hinge domain comprises the amino acid sequence of SEQ ID NO: 21.
21. The composition of claim 20 , wherein the CD8α hinge domain is encoded by a nucleic acid sequence comprising SEQ ID NO: 15.