BCMA-CAR-T cells
View Patent ↗The present invention is directed to a monoclonal anti-human BCMA antibody, or a single-chain variable fragment (scFv), comprising V H having the amino acid sequence of SEQ ID NO: 6 and V L having the amino acid sequence of SEQ ID NO: 7. The present invention is also directed to a BCMA chimeric antigen receptor (CAR) comprising from N-terminus to C-terminus: (i) a single-chain variable fragment (scFv) of the present invention, (ii) a transmembrane domain, (iii) at least one co-stimulatory domains, and (iv) an activating domain. The monoclonal antibody of the present invention exhibits selective and high-affinity binding to BCMA. BCMA CAR-T cells based on BCMA scFv of the present invention significantly decreases multiple myeloma tumor growth in an animal model.
1. A monoclonal anti-human BCMA antibody comprising V H comprising the amino acid sequence of SEQ ID NO: 6 and V L comprising the amino acid sequence of SEQ ID NO: 7.
2. A single-chain variable fragment (scFv) comprising V H comprising the amino acid sequence of SEQ ID NO: 6, and V L comprising the amino acid sequence of SEQ ID NO: 7.
3. The scFv of claim 2 , further comprises a linker in between V H and V L .
4. The scFv of claim 3 , which comprises the amino acid sequence of SEQ ID NO: 5.
5. A chimeric antigen receptor (CAR) comprising from N-terminus to C-terminus:
(i) the scFv of claim 2 ,
(ii) a transmembrane domain,
(iii) at least one co-stimulatory domains, and
(iv) an activating domain.
6. The CAR of claim 5 , wherein the scFv comprises the amino acid sequence of SEQ ID NO: 5.
7. The CAR according to claim 5 , wherein the co-stimulatory domain is CD28, 4-1BB, CD27, or GITR.
8. The CAR according to claim 5 , wherein the co-stimulatory domain is CD28.
9. The CAR according to claim 5 , wherein the activation domain is CD3 zeta.