CAR T-cells against BCMA for the treatment of multiple myeloma
The present invention provides therapeutics for the treatment of Multiple myeloma. In particular, the present invention provides chimeric antigen receptor (CAR) T-cells that can target the B cell maturation antigen.
1 . A chimeric antigen receptor (CAR) comprising an extracellular domain comprising a BCMA targeting-moiety, a transmembrane domain, and an intracellular signaling domain, wherein the BCMA-targeting moiety comprises a VH domain and a VL domain, wherein said VH domain and VL domain consist, respectively, of SEQ ID NO: 1 and SEQ ID NO: 2.
2 . The chimeric antigen receptor of claim 1 , wherein the BCMA-targeting moiety comprises SEQ ID NO: 3.
3 . A chimeric antigen receptor (CAR) comprising an extracellular domain comprising a BCMA targeting-moiety, a transmembrane domain, and an intracellular signaling domain, wherein the BCMA-targeting moiety is a single-chain variable fragment, comprising a VL domain and a VH domain, wherein said VH and VL domains respectively comprise SEQ ID NO: 1 and SEQ ID NO: 2.
4 . The chimeric antigen receptor of claim 3 , wherein the chimeric antigen receptor comprises:
a. the single-chain variable fragment, comprising a VL domain and a VH domain, wherein said VH and VL domains respectively comprise SEQ ID NO: 1 and SEQ ID NO: 2;
b. the transmembrane domain bound to a Hinge domain comprising SEQ ID NO: 9;
c. a costimulatory signaling domain comprising SEQ ID NO: 11; and
d. the intracellular signaling domain comprising SEQ ID NO: 10.
5 . The chimeric antigen receptor (CAR) of claim 4 , wherein the CAR consists of SEQ ID NO: 13.
6 . A nucleic acid encoding the chimeric antigen receptor according to claim 3 .
7 . A cell comprising the nucleic acid according to claim 6 .
8 . The cell according to claim 7 , wherein the cell is a T-cell.
9 . A nucleic acid encoding the chimeric antigen receptor according to claim 1 .
10 . A cell comprising the nucleic acid according to claim 9 .
11 . The cell according to claim 10 , wherein the cell is a T-cell.
12 . A pharmaceutical composition comprising a plurality of cells according to claim 10 and a pharmaceutically acceptable carrier or diluent.
13 . A method of treating multiple myeloma, wherein the method comprises administering the cell of claim 10 , or a pharmaceutical composition comprising the cell, to a patient in need thereof.
14 . The method of claim 13 , wherein the cell is a T-cell.
15 . An immunoglobulin binding protein comprising a BCMA targeting-moiety, wherein the BCMA-targeting moiety comprises a VH domain and a VL domain, wherein said VH domain and VL domain consist, respectively, of SEQ ID NO: 1 and SEQ ID NO: 2.
16 . The immunoglobulin binding protein of claim 15 , wherein the BCMA-targeting moiety comprises SEQ ID NO: 3.
17 . The immunoglobulin binding protein of claim 15 , wherein the BCMA-targeting moiety is an antibody, a single-chain variable fragment, an antigen-binding fragment, a single-chain antigen-binding fragment, or a single-chain fusion protein.