CPC C07K 16/2878 (2013.01) [A61K 35/17 (2013.01); A61P 35/00 (2018.01); C07K 14/7051 (2013.01); C07K 14/70578 (2013.01); C12N 5/0636 (2013.01); A61K 38/00 (2013.01); C07K 2317/565 (2013.01); C07K 2317/622 (2013.01); C07K 2317/732 (2013.01); C07K 2317/76 (2013.01); C07K 2319/02 (2013.01); C07K 2319/03 (2013.01); C07K 2319/30 (2013.01); C07K 2319/33 (2013.01)] | 90 Claims |
1. A method of providing an anti-tumor immunity in a subject having BCMA-expressing cancer cells, the method comprising administering to the subject an effective amount of cells comprising a chimeric antigen receptor (CAR), wherein the CAR comprises an anti-BCMA binding domain, a transmembrane domain, and an intracellular signaling domain comprising a primary signaling domain and a costimulatory signaling domain, wherein:
(a) the anti-BCMA binding domain comprises a heavy chain variable region (VH) comprising a heavy chain complementarity determining region 1 (HC CDR1) of SEQ ID NO: 86, a heavy chain complementarity determining region 2 (HC CDR2) of SEQ ID NO: 87, and a heavy chain complementarity determining region 3 (HC CDR3) of SEQ ID NO: 88, and a light chain variable region (VL) comprising a light chain complementarity determining region 1 (LC CDR1) of SEQ ID NO: 95, a light chain complementarity determining region 2 (LC CDR2) of SEQ ID NO: 96, and a light chain complementarity determining region 3 (LC CDR3) of SEQ ID NO: 97;
(b) the primary signaling domain comprises:
(i) a functional signaling domain of CD3 zeta or FcR gamma; or
(ii) an amino acid sequence having at least 85% sequence identity to SEQ ID NO: 9 or 10; and
(c) the costimulatory signaling domain comprises:
(i) a functional signaling domain of 4-1BB (CD137), OX40, CD2, CD27, CD28, ICAM-1, LFA-1, or ICOS (CD278); or
(ii) an amino acid sequence having at least 85% sequence identity to SEQ ID NO: 7.
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