Monoclonal antibody which specifically recognizes B cell lymphoma and use thereof
Provided is a monoclonal antibody which specifically recognizes B cell lymphoma cells and a use thereof. More specifically, provided are the monoclonal antibody; a pharmaceutical composition for preventing or treating B cell lymphoma including the monoclonal antibody; a composition for diagnosing B cell lymphoma including the monoclonal antibody; a method for providing information for diagnosing B cell lymphoma using the monoclonal antibody; a chimeric antigen receptor (CAR) protein including i) the antibody, ii) a transmembrane domain, and iii) an intracellular signaling domain; a recombinant vector which expresses the CAR protein; a CAR-modified T cell transformed with the recombinant vector; a pharmaceutical composition for preventing or treating B cell lymphoma including the CAR-modified T cell; and an antibody-drug conjugate wherein the monoclonal antibody and a drug are conjugated.
1. A chimeric antigen receptor (CAR) protein, comprising:
i) a monoclonal antibody that binds a B cell lymphoma cell comprising a heavy chain variable region including a heavy chain CDR1 comprising the amino acid sequence of SEQ ID NO: 2; a heavy chain CDR2 comprising the amino acid sequence of SEQ ID NO: 3; and a heavy chain CDR3 comprising the amino acid sequence of SEQ ID NO: 4; and a light chain variable region including a light chain CDR1 comprising the amino acid sequence of SEQ ID NO: 6; a light chain CDR2 comprising the amino acid sequence of SEQ ID NO: 7; and a light chain CDR3 comprising the amino acid sequence of SEQ ID NO: 8;
ii) a transmembrane domain; and
iii) an intracellular signaling domain.
2. The CAR protein of claim 1 , wherein the monoclonal antibody comprises a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 1 and a light chain variable region comprising the amino acid sequence of SEQ ID NO: 5.
3. The CAR protein of claim 1 , wherein the monoclonal antibody is an antibody fragment.
4. The CAR protein of claim 3 , wherein the monoclonal antibody fragment is Fab or scFv.
5. The CAR protein of claim 1 , wherein the intracellular signaling domain is CD3 zeta (ξ) signaling domain.
6. The CAR protein of claim 5 , wherein the intracellular signaling domain further comprises a co-stimulatory domain.
7. The CAR protein of claim 6 , wherein the co-stimulatory domain is derived from a co-stimulatory molecule selected from the group consisting of CD27, CD28, 4-1BB, OX40, CD30, CD40, PD-1, ICOS, LFA-1 (lymphocyte function associated antigen-1), CD2, CD7, LIGHT, NKG2C, B7-H3, and a combination thereof.
8. A recombinant vector comprising a nucleic acid encoding the CAR protein of claim 1 .
9. A pharmaceutical composition for treating B cell lymphoma, comprising a T cell which expresses the CAR protein of claim 1 .
10. A T cell that expresses the CAR protein of claim 1 .
11. The T cell of claim 10 , wherein the T cell is a CD8+ T cell.
12. A pharmaceutical composition comprising the T cell of claim 11 and a pharmaceutically acceptable carrier.
13. The CAR protein of claim 1 , wherein the transmembrane domain comprises a CD8-hinge.
14. The CAR protein of claim 1 comprising an amino acid sequence of SEQ ID NO: 53.
15. A recombinant vector comprising a nucleic acid encoding the CAR protein of claim 14 .
16. A T cell that expresses the CAR protein of claim 14 .
17. The T cell of claim 16 , wherein the T cell is a CD8+ T cell.
18. A pharmaceutical composition comprising the T cell of claim 17 and a pharmaceutically acceptable carrier.