Anti-BCMA antibodies and chimeric antigen receptors
Anti-BCMA antibodies and chimeric antigen receptors (CARs) are provided. Immune cells expressing the anti-BCMA CAR can be used to treat cancer. The anti-BCMA antibodies and CARs can recognize the extracellular domains of human BCMA. The anti-BCMA CAR T cells show specific cytotoxicity towards BCMA-positive target cells.
1 . An anti-BCMA antibody, or an antigen-binding portion thereof, comprising a light chain variable region (V L ) and a heavy chain variable region (V H ), wherein the light chain variable region comprises three CDRs, CDR1, CDR2 and CDR3, having amino acid sequences comprising the amino acid sequences set forth in SEQ ID NOs: 118, 119 and 120, respectively; and wherein the heavy chain variable region comprises three complementarity determining regions (CDRs), CDR1, CDR2 and CDR3, having amino acid sequences comprising the amino acid sequences set forth in SEQ ID NOs: 121, 122 and 123, respectively.
2 . An anti-BCMA antibody or antigen-binding portion thereof, comprising a light chain variable region (V L ) and a heavy chain variable region (V H ), wherein the V L and V H have amino acid sequences comprising the amino acid sequences set forth in SEQ ID NO: 67 and SEQ ID NO: 68, respectively.
3 . The antibody or antigen-binding portion thereof of claim 1 , wherein the antibody or antigen-binding portion thereof is selected from the group consisting of: (a) a whole immunoglobulin molecule; (b) an scFv; (c) a Fab fragment; (d) an F(ab′)2; and (e) a disulfide linked Fv.
4 . A composition comprising the antibody or antigen-binding portion thereof of claim 1 , and a pharmaceutically acceptable carrier.
5 . A chimeric antigen receptor (CAR), comprising an anti-BCMA antigen-binding region which comprises a light chain variable region (V L ) and a heavy chain variable region (V H ),
the V L comprising three CDRs, CDR1, CDR2 and CDR3, having amino acid sequences comprising the amino acid sequences set forth in SEQ ID NOs: 118, 119 and 120, respectively; the V H comprising three complementarity determining regions (CDRs), CDR1, CDR2 and CDR3, having amino acid sequences comprising the amino acid sequences set forth in SEQ ID NOs: 121, 122 and 123, respectively.
6 . A chimeric antigen receptor (CAR), comprising an anti-BCMA antigen-binding region which comprises a light chain variable region (V L ) and a heavy chain variable region (V H ), wherein the V L and V H have amino acid sequences comprising the amino acid sequences set forth in SEQ ID NO: 67 and SEQ ID NO: 68, respectively.
7 . The CAR of claim 5 , wherein the anti-BCMA antigen-binding region is a single-chain variable fragment (scFv) that specifically binds BCMA.
8 . The CAR of claim 5 , wherein the CAR further comprises one or more of the following:
(a) a signal peptide,
(b) a hinge region,
(c) a transmembrane domain,
(d) a co-stimulatory region, and
(e) a cytoplasmic signaling domain.
9 . The CAR of claim 8 , wherein the co-stimulatory region comprises a co-stimulatory region of 4-1BB (CD137), CD28, OX40, CD2, CD7, CD27, CD30, CD40, CD70, CD134, PD1, Dap10, CDS, ICAM-1, LFA-1 (CD11a/CD18), ICOS (CD278), NKG2D, GITR, TLR2, or combinations thereof.
10 . The CAR of claim 8 , wherein the cytoplasmic signaling domain comprises a cytoplasmic signaling domain of CD3ζ.
11 . The CAR of claim 8 , wherein the hinge region comprises a hinge region of Ig4, CD8, CD28, CD137, or combinations thereof.
12 . The CAR of claim 8 , wherein the transmembrane domain comprises a transmembrane domain of CD8, CD28, CD3ε, CD45, CD4, CD5, CD9, CD16, CD22, CD33, CD37, CD64, CD80, CD86, CD134, CD137, CD154, or combinations thereof.
13 . An immune cell expressing the CAR of claim 5 .
14 . The immune cell of claim 13 , wherein the immune cell is a T cell, a natural killer (NK) cell, a natural killer T cell, a lymphoid progenitor cell, a hematopoietic stem cell, a stem cell, a macrophage, or a dendritic cell.