BCMA CHIMERIC ANTIGEN RECEPTORS
The invention provides improved compositions for adoptive T cell therapies for B cell related conditions.
1 .- 65 . (canceled)
66 . 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 amino acids 22-493 of the amino acid sequence set forth in SEQ ID NO: 9.
67 . The method of claim 66 , wherein the B cell malignancy is multiple myeloma (MM).
68 . The method of claim 67 , wherein the MM is selected from overt multiple myeloma, smoldering multiple myeloma, plasma cell leukemia, non-secretory myeloma, IgD myeloma, osteosclerotic myeloma, solitary plasmacytoma of bone, and extramedullary plasmacytoma.
69 . The method of claim 66 , wherein the B cell malignancy is non-Hodgkin's lymphoma (NHL).
70 . The method of claim 69 , wherein the NHL is selected from 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.
71 . The method of claim 66 , wherein the immune effector cells comprise T lymphocytes.
72 . The method of claim 66 , wherein the immune effector cells comprise natural killer (NK) cells.
73 . The method of claim 66 , wherein the immune effector cells are administered parenterally.
74 . The method of claim 66 , wherein the immune effector cells are administered intravenously.
75 . 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 encodes a CAR comprising amino acids 22-493 of the amino acid sequence set forth in SEQ ID NO: 9.
76 . The method of claim 75 , wherein the B cell malignancy is multiple myeloma (MM).
77 . The method of claim 76 , wherein the MM is selected from overt multiple myeloma, smoldering multiple myeloma, plasma cell leukemia, non-secretory myeloma, IgD myeloma, osteosclerotic myeloma, solitary plasmacytoma of bone, and extramedullary plasmacytoma.
78 . The method of claim 75 , wherein the B cell malignancy is non-Hodgkin's lymphoma (NHL).
79 . The method of claim 78 , wherein the NHL is selected from 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.
80 . The method of claim 75 , wherein the immune effector cells comprise T lymphocytes.
81 . The method of claim 75 , wherein the immune effector cells comprise natural killer (NK) cells.
82 . The method of claim 75 , wherein the vector is an episomal vector.
83 . The method of claim 75 , wherein the vector is a viral vector.
84 . The method of claim 75 , wherein the vector is a retroviral vector.
85 . The method of claim 75 , wherein the vector is a lentiviral vector.
86 . The method of claim 75 , wherein the immune effector cells are administered parenterally.
87 . The method of claim 75 , wherein the immune effector cells are administered intravenously.
88 . 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 comprising amino acids 22-493 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.
89 . The method of claim 88 , wherein the immune effector cells comprise T lymphocytes.
90 . The method of claim 88 , wherein the immune effector cells comprise natural killer (NK) cells.
91 . The method of claim 88 , wherein the composition comprises a cryoprotective agent.
92 . The method of claim 88 , wherein the lentiviral vector is derived from human immunodeficiency virus (HIV).
93 . The method of claim 88 , wherein the lentiviral vector is derived from HIV-1.
94 . The method of claim 88 , wherein the B cell malignancy is multiple myeloma (MM).
95 . The method of claim 94 , wherein the MM is selected from overt multiple myeloma, smoldering multiple myeloma, plasma cell leukemia, non-secretory myeloma, IgD myeloma, osteosclerotic myeloma, solitary plasmacytoma of bone, and extramedullary plasmacytoma.
96 . The method of claim 88 , wherein the B cell malignancy is non-Hodgkin's lymphoma (NHL).
97 . The method of claim 96 , wherein the NHL is selected from 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.
98 . The method of claim 88 , wherein the B cell malignancy is a plasma cell malignancy.
99 . 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 CAR comprising amino acids 22-493 of the amino acid sequence set forth in SEQ ID NO: 9.
100 . The method of claim 99 , wherein the MM is selected from overt multiple myeloma, smoldering multiple myeloma, plasma cell leukemia, non-secretory myeloma, IgD myeloma, osteosclerotic myeloma, solitary plasmacytoma of bone, and extramedullary plasmacytoma.
101 . The method of claim 99 , wherein the immune effector cells comprise a lentiviral vector that comprises a polynucleotide encoding the CAR.
102 . The method of claim 101 , 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, d1587rev 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.
103 . The method of claim 99 , wherein the immune effector cells are administered parenterally.
104 . The method of claim 99 , wherein the immune effector cells are administered intravenously.
105 . 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 CAR comprising:
a) means for binding B cell maturation antigen (BCMA) and;
b) amino acids 271-493 of the amino acid sequence set forth in SEQ ID NO: 9.