BCMA-specific antibody and chimeric antigen receptor
An embodiment relates to an anti-BCMA-binding protein and, more specifically, provides an isolated BCMA-binding protein comprising an antigen-binding domain that binds specifically to BCMA, wherein the antigen-binding domain comprises: i) heavy chain variable domain complementarity determining region 1 (VH-CDR1) comprising the amino acid sequence of SEQ ID NO: 1 or an amino acid sequence having at least 80% homology to SEQ ID NO: 1; ii) VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 2 or an amino acid sequence having at least 80% homology to SEQ ID NO: 2; and iii) VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 3 or an amino acid sequence having at least 80% homology to SEQ ID NO: 3.
1 . An isolated BCMA (B-cell maturation antigen)-binding protein, comprising:
an antigen-binding domain that binds specifically to BCMA, wherein the antigen-binding domain comprises:
i) heavy chain variable domain complementarity determining region 1 (VH-CDR1) comprising the amino acid sequence of SEQ ID NO: 1;
ii) VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 2;
iii) VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 3;
iv) light chain variable domain complementarity determining region 1 (VL-CDR1) comprising the amino acid sequence of SEQ ID NO: 4;
v) VL-CDR2 comprising the amino acid sequence of SEQ ID NO: 5; and
vi) VL-CDR3 comprising the amino acid sequence of SEQ ID NO: 6.
2 . The isolated BCMA-binding protein of claim 1 , wherein the isolated BCMA-binding protein comprises:
a heavy chain variable domain (VH) comprising the amino acid sequence of SEQ ID NO: 7; and
a light chain variable domain (VL) comprising the amino acid sequence of SEQ ID NO: 8.
3 . The isolated BCMA-binding protein of claim 2 , wherein the isolated BCMA-binding protein further comprises a linker, and the linker, the VH and the VL are arranged in any one order selected from among VH-linker-VL and VL-linker-VH, in a N-terminal to C-terminal direction.
4 . The isolated BCMA-binding protein of claim 1 , wherein the isolated BCMA-binding protein comprises the amino acid sequence of SEQ ID NO: 9.
5 . The isolated BCMA-binding protein of claim 1 , wherein the isolated BCMA-binding protein is an scFv.
6 . The isolated BCMA-binding protein of claim 5 , wherein the isolated BCMA-binding protein is incorporated into an anti-BCMA chimeric antigen receptor, wherein the anti-BCMA chimeric antigen receptor further comprises an intracellular signaling domain, wherein the intracellular signaling domain comprises a signaling domain derived from any one or more selected from a group consisting of CD3ζ, FcγR, ICOS (CD278), 4-1BB (CD137), OX40 (CD134), CD27, CD28, IL-2Rβ, IL-15R-α, CD40, MyD88, DAP10, DAP12, MHC class I molecules, TNF receptor proteins, immunoglobulin-like proteins, cytokine receptors, integrins, SLAM protein, activating NK cell receptors, BTLA, and Toll ligand receptors.
7 . The isolated BCMA-binding protein of claim 6 , wherein the anti-BCMA chimeric antigen receptor further comprises a transmembrane domain, wherein the transmembrane domain is derived from any one selected from among T-cell receptor (TCR) α chains, TCR β chains, CD3ζ, CD3ε, CD28, CD45, CD4, CD5, CD8, CD9, CD16, CD22, CD33, CD37, CD64, CD80, CD86, CD134, CD137, CD154, CD278, and CD314.
8 . The isolated BCMA-binding protein of claim 6 , wherein the anti-BCMA chimeric antigen receptor further comprises a hinge domain, wherein the hinge domain is located between the BCMA-binding protein and the transmembrane domain and is derived from any one selected from among CD8, FcγIIIα, and IgG1.
9 . The isolated BCMA-binding protein of claim 6 , wherein the anti-BCMA chimeric antigen receptor further comprises a signal peptide at the N-terminus, wherein the signal peptide is derived from any one selected from among CD8, IgG1 heavy chains, IgK light chains, and GM-CSF.
10 . The isolated BCMA-binding protein of claim 6 , wherein the anti-BCMA chimeric antigen receptor comprises the amino acid sequence of SEQ ID NO: 15 or an amino acid sequence having at least 80% homology to SEQ ID NO: 15.