Anti-BCMA antibodies and uses thereof
Provided herein are antibodies that immunospecifically bind to BCMA. Also described are related polynucleotides capable of encoding the provided BCMA-specific antibodies or antigen-binding fragments, cells expressing the provided antibodies or antigen-binding fragments, as well as associated vectors and detectably labeled antibodies or antigen-binding fragments. In addition, methods of using the provided antibodies are described. For example, the provided antibodies may be used to diagnose, treat, or monitor BCMA-expressing cancer progression, regression, or stability; to determine whether or not a patient should be treated for cancer; or to determine whether or not a subject is afflicted with BCMA-expressing cancer and thus may be amenable to treatment with a BCMA-specific anti-cancer therapeutic, such as the multispecific antibodies against BCMA and CD3 described herein.
1. A recombinant antibody, or an antigen-binding fragment thereof, that binds immunospecifically to BCMA, wherein the antibody has a heavy chain and a light chain, said heavy chain and light chain comprising:
a heavy chain complementarity determining region 1 (CDR1) having the amino acid sequence of SEQ ID NO: 4, a heavy chain CDR2 having the amino acid sequence of SEQ ID NO: 5, and a heavy chain CDR3 having the amino acid sequence of SEQ ID NO: 6, a light chain CDR1 having the amino acid sequence of SEQ ID NO: 24, a light chain CDR2 having the amino acid sequence of SEQ ID NO: 25, and a light chain CDR3 having the amino acid sequence of SEQ ID NO: 26.
2. The antibody or antigen-binding fragment of claim 1 , wherein the heavy chain of the antibody comprises the amino acid sequence of SEQ ID NO: 27, and the light chain of the antibody comprises the amino acid sequence of SEQ ID NO:28.
3. The antibody or antigen-binding fragment of any one of claims 1 and 2 , wherein the antibody or antigen-binding fragment thereof binds to the extracellular domain of human BCMA.
4. The antibody or antigen-binding fragment of any one of claims 1 and 2 , wherein the antibody or antigen-binding fragment is a human antibody or antigen-binding fragment.
5. The antigen binding fragment of any one of claims 1 and 2 , wherein the antigen binding fragment is a Fab fragment, a Fab2 fragment, or a single chain antibody.
6. The antibody or antigen-binding fragment of any one of claims 1 and 2 , wherein the antibody or antigen-binding fragment thereof inhibits the interaction of BCMA and APRIL.
7. The antibody or antigen-binding fragment of claim 6 , wherein the antibody or antigen-binding fragment exhibits an IC 50 for the interaction of BCMA and APRIL of about 5.9 nM as measured by ELISA.
8. The antibody or antigen-binding fragment of any one of claims 1 and 2 , wherein the antibody or antigen-binding fragment thereof is an IgG.
9. The antibody or antigen-binding fragment of any one of claims 1 and 2 , is an IgG4 isotype.
10. The antibody of claim 9 wherein the IgG4 has a S228P substitution, a L234A substitution and a L235A substitution in its Fc region.
11. The antibody or antigen-binding fragment of any one of claims 1 and 2 , wherein the antibody or antigen-binding fragment thereof immunospecifically binds human BCMA and cross reacts to cynomolgus monkey BCMA.
12. The antibody or antigen-binding fragment of any one of claims 1 and 2 , wherein the antibody or antigen-binding fragment thereof binds BCMA on the surface of human myeloma cells.
13. The antibody or antigen-binding fragment of any one of claims 1 and 2 , wherein the antibody or antigen-binding fragment thereof binds BCMA on the surface of human multiple myeloma cells.
14. A recombinant cell expressing the antibody or antigen-binding fragment of any one of claims 1 and 2 .
15. The cell of claim 14 wherein the cell is a hybridoma.
16. The cell of claim 14 wherein the antibody is recombinantly produced.