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 modified autologous 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, a transmembrane domain, a CD27 costimulatory signaling region, and a CD3 zeta signaling domain.
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 2 , 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 the CD19 antigen binding domain is an antibody or an antigen-binding fragment thereof.
5. The composition of claim 4 , wherein the antigen binding fragment is a Fab or scFv.
6. The composition of claim 5 , wherein the antigen binding fragment is an scFv.
7. The composition of claim 6 , wherein the scFv comprises the amino acid sequence of SEQ ID NO: 20.
8. The composition of claim 1 , wherein the transmembrane domain is CD8α transmembrane domain.
9. The composition of claim 8 , wherein the CD8α transmembrane domain comprises the amino acid sequence of SEQ ID NO: 22.
10. The composition of claim 1 , wherein the CAR further comprises a hinge domain.
11. The composition of claim 10 , wherein the hinge domain is a CD8α hinge domain.
12. The composition of claim 11 , wherein the CD8α hinge domain comprises the amino acid sequence of SEQ ID NO: 21.
13. The composition of claim 1 , wherein the CD3 zeta signaling domain comprises the amino acid sequence of SEQ ID NO: 24.
14. The composition of claim 6 , wherein the scFv is encoded by a nucleic acid sequence comprising SEQ ID NO: 14.
15. The composition of claim 8 , wherein the CD8α transmembrane domain is encoded by a nucleic acid sequence comprising SEQ ID NO: 16.
16. The composition of claim 1 , wherein the CD3 zeta signaling domain is encoded by a nucleic acid sequence comprising SEQ ID NO: 18.
17. The composition of claim 11 , wherein the hinge domain is encoded by a nucleic acid sequence comprising SEQ ID NO:15.