CS1 antibody and anti-CS1-CAR-t cells
The present invention is directed to a monoclonal anti-human CS1 antibody or a single-chain variable fragment (scFv), comprising VH having the amino acid of SEQ ID NO: 3 and VL having the amino acid of SEQ ID NO: 7. The present invention is also directed to a chimeric antigen receptor fusion protein 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.
1. A monoclonal anti-human CS1 antibody comprising a heavy chain variable domain (VH) having the amino acid sequence of SEQ ID NO: 3 and a light chain variable domain (VL) having the amino acid sequence of SEQ ID NO: 7.
2. A single-chain variable fragment (scFv) comprising a VH having the amino acid sequence of SEQ ID NO: 3 and a VL having the amino acid sequence of SEQ ID NO: 7.
3. The scFv of claim 2 , further comprising a linker in between the VH and the VL.
4. The scFv of claim 3 , which has the amino acid sequence of SEQ ID NO: 8.
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 domain, and
(iv) an activating domain.
6. The CAR of claim 5 , wherein the scFv has the amino acid sequence of SEQ ID NO: 8.
7. The CAR according to claim 5 , wherein the co-stimulatory domain is a CD28 or a 4-1BB co-stimulatory domain.
8. The CAR according to claim 5 , wherein the activating domain is a CD3 zeta activating domain.
9. The CAR of claim 5 , which has the amino acid sequence of SEQ ID NO: 20.
10. The CAR of claim 5 , which has the amino acid sequence of SEQ ID NO: 22.
11. A nucleic acid encoding the CAR of claim 5 .
12. A T cell or natural killer cell modified to express the CAR of claim 5 .