BCMA chimeric antigen receptors and uses thereof
AssigneeNovartis AG
InventorsAida Abujoub, John Blankenship, Dexiu Bu, Tony Fleming, Brian Holmberg, Connie Hong, Lu Huang, Chonghui Zhang
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Abstract
The invention provides compositions and methods for treating diseases associated with expression of BCMA. The invention also relates to chimeric antigen receptor (CAR) specific to BCMA, vectors encoding the same, and recombinant T cells comprising the BCMA CAR. The invention also includes methods of administering a genetically modified T cell expressing a CAR that comprises a BCMA binding domain.
Claims17
An isolated chimeric antigen receptor (CAR) comprising an anti-BCMA binding domain, a transmembrane domain, and an intracellular signaling domain comprising a primary signaling domain and a costimulatory signaling domain, wherein 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, 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, wherein:
- (a) the primary signaling domain:
- (i) comprises a functional signaling domain of CD3 zeta or FcR gamma;
- or
- (ii) comprises the amino acid sequence of SEQ ID NO:
- 9 or 10, or an amino acid sequence having at least about 85%, 90%, 95%, or 99% sequence identity thereto;
- and
- (b) the costimulatory signaling domain:
- (i) comprises a functional signaling domain of 4-1BB (CD137), OX40, CD2, CD27, CD28, ICAM-1, LFA-1, or ICOS (CD278);
- or
- (ii) comprises the amino acid sequence of SEQ ID NO:
- 7, or an amino acid sequence having at least about 85%, 90%, 95%, or 99% sequence identity thereto.
An anti-BCMA binding domain comprising 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.
A chimeric antigen receptor (CAR) that binds to BCMA, comprising, from N-terminus to C-terminus:
- (i) leader sequence of SEQ ID NO:
- 1;
- (ii) a HC CDR1 of SEQ ID NO:
- 86;
- (iii) a HC CDR2 of SEQ ID NO:
- 87;
- (iv) a HC CDR3 of SEQ ID NO:
- 88;
- (v) a LC CDR1 of SEQ ID NO:
- 95;
- (vi) a LC CDR2 of SEQ ID NO:
- 96;
- (vii) a LC CDR3 of SEQ ID NO:
- 97;
- (viii) a CD8 transmembrane domain and hinge of SEQ ID NO:
- 202;
- (ix) a functional signaling domain of 4-1BB of SEQ ID NO:
- 7;
- and
- (x) a functional signaling domain of CD3 zeta of SEQ ID NO:
- 10.
Dependencies are inferred from the claim text.