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 human 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) encoded by the polynucleotide sequence set forth in SEQ ID NO: 10.
2. The method of claim 1 , wherein the B cell malignancy is multiple myeloma (MM) or non-Hodgkin's lymphoma (NHL).
3. The method of claim 1 , wherein the immune effector cells comprise T lymphocytes or natural killer (NK) cells.
4. The method of claim 1 , wherein the immune effector cells are comprised within a pharmaceutical composition, wherein the composition further comprises a pharmaceutically acceptable excipient.
5. The method of claim 4 , wherein the composition further comprises a cryoprotective agent.
6. The method of claim 1 , wherein the immune effector cells are administered intravenously.
7. A method of treating a B cell malignancy in a human 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 encoded by the polynucleotide sequence set forth in SEQ ID NO: 10.
8. The method of claim 7 , wherein the B cell malignancy is multiple myeloma (MM) or non-Hodgkin's lymphoma (NHL).
9. The method of claim 7 , wherein the immune effector cells comprise T lymphocytes or natural killer (NK) cells.
10. The method of claim 7 , wherein the vector is an episomal vector, a viral vector, a retroviral vector, or a lentiviral vector.
11. The method of claim 7 , wherein the immune effector cells are administered intravenously.
12. A method of treating a B cell malignancy in a human 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 long terminal repeat (LTR) wherein the promoter of the 5′ LTR is replaced with a CMV promoter;
a Psi (Ψ) packaging signal;
a central polypurine tract/DNA flap (cPPT/FLAP);
a Rev response element (RRE);
a myeloproliferative sarcoma virus enhancer, negative control region deleted, d1587rev primer-binding site substituted (MND) promoter operably linked to a polynucleotide comprising the sequence set forth in SEQ ID NO: 10;
a right (3′) lentiviral self-inactivating (SIN) LTR; and
a heterologous polyadenylation sequence.
13. The method of claim 12 , wherein the immune effector cells comprise T lymphocytes or natural killer (NK) cells.
14. The method of claim 12 , wherein the composition further comprises a cryoprotective agent.
15. The method of claim 12 , wherein the lentiviral vector is derived from human immunodeficiency virus (HIV).
16. The method of claim 12 , wherein the lentiviral vector is derived from HIV-1.
17. The method of claim 12 , wherein the B cell malignancy is multiple myeloma (MM).
18. The method of claim 17 , 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.
19. The method of claim 12 , wherein the B cell malignancy is non-Hodgkin's lymphoma (NHL).
20. The method of claim 19 , 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.
21. The method of claim 12 , wherein the B cell malignancy is a plasma cell malignancy.
22. The method of claim 12 , wherein the immune effector cells are administered intravenously.
23. A method of treating multiple myeloma (MM) in a human 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) encoded by the polynucleotide sequence set forth in SEQ ID NO: 10.
24. The method of claim 23 , wherein the MINI 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.
25. The method of claim 23 , wherein the immune effector cells comprise T lymphocytes or natural killer (NK) cells.
26. The method of claim 23 , wherein the immune effector cells are comprised within a pharmaceutical composition, wherein the composition further comprises a pharmaceutically acceptable excipient.
27. The method of claim 23 , wherein the immune effector cells comprise a lentiviral vector that comprises a polynucleotide encoding the CAR.
28. The method of claim 23 , wherein the immune effector cells are administered intravenously.
29. The method of claim 1 , wherein the immune effector cells comprise T lymphocytes.
30. The method of claim 29 , wherein the immune effector cells are autologous immune effector cells.
31. The method of claim 30 , wherein the B cell malignancy is multiple myeloma (MM).
32. The method of claim 7 , wherein the immune effector cells comprise T lymphocytes.
33. The method of claim 32 , wherein the immune effector cells are autologous immune effector cells.
34. The method of claim 33 , wherein the B cell malignancy is multiple myeloma (MM).
35. The method of claim 12 , wherein the immune effector cells comprise T lymphocytes.
36. The method of claim 35 , wherein the immune effector cells are autologous immune effector cells.
37. The method of claim 36 , wherein the B cell malignancy is multiple myeloma (MM).
38. The method of claim 23 , wherein the immune effector cells comprise T lymphocytes.
39. The method of claim 38 , wherein the immune effector cells are autologous immune effector cells.