Compositions and 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 cell comprising a lentiviral vector comprising a nucleic acid sequence encoding a chimeric antigen receptor (CAR), the CAR comprising a CD19 antigen binding domain comprising the amino acid sequence of SEQ ID NO: 20, a transmembrane domain, a costimulatory signaling region comprising 4-1BB, and a CD3 zeta signaling domain, wherein the cell is from a human having cancer.
2. The cell of claim 1 , wherein the CAR comprises the amino acid sequence of SEQ ID NO: 12.
3. The cell of claim 1 , wherein the nucleic acid comprises the nucleic acid sequence of SEQ ID NO: 8.
4. The cell of claim 1 , wherein the CD19 antigen binding domain is an antibody or an antigen-binding fragment thereof.
5. The cell of claim 4 , wherein the CD19 antigen-binding fragment is a Fab or a scFv.
6. The cell of claim 1 , wherein the cell is a T cell or a Natural Killer (NK) cell.
7. The cell of claim 6 , wherein the cell is a T cell.
8. The cell of claim 1 , wherein the cell exhibits an anti-tumor immunity.
9. The cell of claim 1 , wherein the vector comprises a promoter.
10. The cell of claim 1 , wherein the promoter is an EF-1α promoter.
11. A method of stimulating a T cell-mediated immune response to a CD19 expressing target cell population in a human, the method comprising administering to the human a pharmaceutical composition comprising an effective amount of a population of cells comprising a lentiviral vector, wherein the lentiviral vector comprises a nucleic acid encoding a CAR, wherein the CAR comprises a CD19 antigen binding domain comprising the amino acid sequence of SEQ ID NO: 20, a transmembrane domain, a costimulatory signaling region comprising 4-1BB, and a CD3 zeta signaling domain, wherein the cells are from a human having cancer.
12. The method of 11 , wherein the cells comprising the lentiviral vector are T cells.
13. A method of providing an anti-tumor immunity in a human, the method comprising administering to the human a pharmaceutical composition comprising an effective amount of a population of cells comprising a lentiviral vector, wherein the lentiviral vector comprises a nucleic acid encoding a CAR, wherein the CAR comprises a CD19 antigen binding domain comprising the amino acid sequence of SEQ ID NO: 20, a transmembrane domain, a costimulatory signaling region comprising 4-1BB, and a CD3 zeta signaling domain, wherein the cells are from a human having cancer.
14. The method of claim 13 , wherein the cells comprising the lentiviral vector are T cells.
15. A method of treating a hematological cancer in a human comprising administering to the human a pharmaceutical composition comprising an effective amount of a population of cells comprising a lentiviral vector, wherein the lentiviral vector comprises a nucleic acid encoding a CAR, wherein the CAR comprises a CD19 antigen binding domain comprising the amino acid sequence of SEQ ID NO: 20, a transmembrane domain, a costimulatory signaling region comprising 4-1BB, and a CD3 zeta signaling domain, wherein the cells are from a human having cancer.
16. The method of 15 , wherein the hematological cancer is leukemia or lymphoma.
17. The method of 16 , wherein the hematological cancer is mantle cell lymphoma, diffuse large B cell lymphoma, multiple myeloma, Hodgkin's disease, or non-Hodgkin's lymphoma.
18. The method of 15 , wherein the hematological cancer is resistant to chemotherapy.
19. The method of claim 15 , wherein the cells comprising the lentiviral vector are T cells.
20. The method of claim 15 , wherein the pharmaceutical composition further comprises a pharmaceutically acceptable carrier, diluent or excipient.
21. The method of claim 15 , wherein the pharmaceutical composition comprises a buffer.
22. The method of claim 21 , wherein the buffer is neutral buffer saline or phosphate buffered saline.
23. The method of claim 15 , wherein the pharmaceutical composition further comprises a carbohydrate.
24. The method of claim 23 , wherein the carbohydrate is selected from glucose, mannose, sucrose, dextran and mannitol.
25. The method of claim 15 , wherein the pharmaceutical composition further comprises an infusible cryomedia.
26. The method of claim 25 , wherein the infusible cryomedia comprises plasmalyte A, dextrose, NaCl, DMSO, dextran and human serum albumin.
27. The method of claim 15 , wherein the treating further comprises a bone marrow or stem cell transplant.
28. The method of claim 15 , wherein a chemotherapy designed for depletion of lymphocytes is administered to the human prior to administration of the pharmaceutical composition.
29. The method of claim 15 , further comprising administering one or more cytokines to the human.
30. The method of claim 29 , wherein the cytokine is IL-2 or IL-15.