BCMA chimeric antigen receptors
The invention provides improved compositions for adoptive T cell therapies for B cell related conditions.
1. A method of treating a B cell malignancy in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of human immune effector cells that express a chimeric antigen receptor (CAR) comprising the amino acid sequence set forth in SEQ ID NO: 9.
2. The method of claim 1 , wherein the B cell malignancy is multiple myeloma (MM).
3. The method of claim 1 , wherein the B cell malignancy is non-Hodgkin's lymphoma (NHL).
4. The method of claim 1 , wherein the immune effector cells comprise T lymphocytes.
5. The method of claim 1 , wherein the immune effector cells comprise natural killer (NK) cells.
6. The method of claim 1 , wherein the immune effector cells are comprised within a pharmaceutical composition.
7. The method of claim 6 , wherein the composition further comprises a pharmaceutically acceptable excipient.
8. The method of claim 6 , wherein the composition further comprises a cryoprotective agent.
9. The method of claim 1 , wherein the immune effector cells are administered parenterally.
10. The method of claim 1 , wherein the immune effector cells are administered intravenously.
11. A method of treating a B cell malignancy in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of a composition comprising a pharmaceutically acceptable excipient and human immune effector cells that express a chimeric antigen receptor (CAR) consisting of the amino acid sequence set forth in SEQ ID NO: 9.
12. The method of claim 11 , wherein the B cell malignancy is multiple myeloma (MM).
13. The method of claim 11 , wherein the B cell malignancy is non-Hodgkin's lymphoma (NHL).
14. The method of claim 11 , wherein the immune effector cells comprise T lymphocytes.
15. The method of claim 11 , wherein the immune effector cells comprise natural killer (NK) cells.
16. The method of claim 11 , wherein the composition further comprises a cryoprotective agent.
17. The method of claim 11 , wherein the immune effector cells are administered parenterally.
18. The method of claim 11 , wherein the immune effector cells are administered intravenously.
19. A method of treating a B cell malignancy in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of human immune effector cells comprising a vector comprising a polynucleotide that expresses a CAR consisting of the amino acid sequence set forth in SEQ ID NO: 9.
20. The method of claim 19 , wherein the B cell malignancy is multiple myeloma (MM).
21. The method of claim 19 , wherein the B cell malignancy is non-Hodgkin's lymphoma (NHL).
22. The method of claim 19 , wherein the immune effector cells comprise T lymphocytes.
23. The method of claim 19 , wherein the immune effector cells comprise natural killer (NK) cells.
24. The method of claim 19 , wherein the human immune effector cells are comprised within a composition, wherein the composition comprises a cryoprotective agent.
25. The method of claim 19 , wherein the vector is an episomal vector.
26. The method of claim 19 , wherein the vector is a viral vector.
27. The method of claim 19 , wherein the vector is a retroviral vector.
28. The method of claim 19 , wherein the vector is a lentiviral vector.
29. The method of claim 19 , wherein the immune effector cells are administered parenterally.
30. The method of claim 19 , wherein the immune effector cells are administered intravenously.
31. A method of treating a B cell malignancy in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of a composition comprising a physiologically acceptable excipient and human immune effector cells;
wherein the immune effector cells comprise a lentiviral vector;
wherein the lentiviral vector comprises a left (5′) lentiviral LTR wherein the promoter of the 5′ LTR is replaced with a CMV promoter; a Psi (Ψ) packaging signal; a cPPT/FLAP; a Rev response element (RRE); a myeloproliferative sarcoma virus enhancer, negative control region deleted, dl587rev primer-binding site substituted (MND) promoter operably linked to a polynucleotide encoding a CAR consisting of the amino acid sequence set forth in SEQ ID NO: 9; a right (3′) lentiviral self-inactivating (SIN) LTR; and a heterologous polyadenylation sequence.
32. The method of claim 31 , wherein the immune effector cells comprise T lymphocytes.
33. The method of claim 31 , wherein the immune effector cells comprise natural killer (NK) cells.
34. The method of claim 31 , wherein the composition further comprises a cryoprotective agent.
35. The method of claim 31 , wherein the lentiviral vector is derived from human immunodeficiency virus (HIV).
36. The method of claim 31 , wherein the lentiviral vector is derived from HIV-1.
37. The method of claim 31 , wherein the B cell malignancy is multiple myeloma (MM).
38. The method of claim 37 , wherein the MM is selected from the group consisting of: overt multiple myeloma, smoldering multiple myeloma, plasma cell leukemia, non-secretory myeloma, IgD myeloma, osteosclerotic myeloma, solitary plasmacytoma of bone, and extramedullary plasmacytoma.
39. The method of claim 31 , wherein the B cell malignancy is non-Hodgkin's lymphoma (NHL).
40. The method of claim 39 , wherein the NHL is selected from the group consisting of: Burkitt lymphoma, chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), diffuse large B-cell lymphoma, follicular lymphoma, immunoblastic large cell lymphoma, precursor B-lymphoblastic lymphoma, and mantle cell lymphoma.
41. The method of claim 31 , wherein the B cell malignancy is a plasma cell malignancy.
42. A method of treating multiple myeloma (MM) in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of human immune effector cells that express a chimeric antigen receptor (CAR) consisting of the amino acid sequence set forth in SEQ ID NO: 9.
43. The method of claim 42 , wherein the MM is selected from the group consisting of: overt multiple myeloma, smoldering multiple myeloma, plasma cell leukemia, non-secretory myeloma, IgD myeloma, osteosclerotic myeloma, solitary plasmacytoma of bone, and extramedullary plasmacytoma.
44. The method of claim 42 , wherein the immune effector cells are comprised within a pharmaceutical composition.
45. The method of claim 44 , wherein the composition further comprises a pharmaceutically acceptable excipient.
46. The method of claim 44 , wherein the composition further comprises a cryoprotective agent.
47. The method of claim 42 , wherein the immune effector cells comprise a lentiviral vector that comprises a polynucleotide encoding the CAR.
48. The method of claim 47 , wherein the lentiviral vector comprises a left (5′) lentiviral LTR wherein the promoter of the 5′ LTR is replaced with a CMV promoter; a Psi (Ψ) packaging signal; a cPPT/FLAP; a Rev response element (RRE); a myeloproliferative sarcoma virus enhancer, negative control region deleted, dl587rev primer-binding site substituted (MND) promoter operably linked to the polynucleotide encoding the CAR; a right (3′) lentiviral self-inactivating (SIN) LTR; and a heterologous polyadenylation sequence.
49. The method of claim 42 , wherein the immune effector cells are administered parenterally.
50. The method of claim 42 , wherein the immune effector cells are administered intravenously.