Anti-GPRC5D antibodies, bispecific antigen binding molecules that bind GPRC5D and CD3, and uses thereof
Provided herein are antibodies that specifically bind to GPRC5D. Also described are related polynucleotides capable of encoding the provided GPRC5D-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 GPRC5D-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 GPRC5D-expressing cancer and thus may be amenable to treatment with a GPRC5D-specific anti-cancer therapeutic, such as the multispecific antibodies against GPRC5D and CD3 described herein.
1. An isolated GPRC5D x CD3 bispecific antibody comprising:
a) a first heavy chain (HC1);
b) a second heavy chain (HC2);
c) a first light chain (LC 1); and
d) a second light chain (LC2),
wherein the HC1 and the LC1 pair to form a first antigen-binding site that specifically binds CD3, and the HC2 and the LC2 pair to form a second antigen-binding site that specifically binds GPRC5D;
wherein the HC1 comprises the amino acid sequence of SEQ ID NO: 25 and the LC1 comprises the amino acid sequence of SEQ ID NO: 26, and
wherein the HC2 comprises the amino acid sequence of SEQ ID NO: 55 and the LC2 comprises the amino acid sequence of SEQ ID NO: 58.
2. The GPRC5D x CD3 bispecific antibody of claim 1 , wherein the bispecific antibody is of IgG1, IgG2, IgG3, or IgG4 isotype.
3. The GPRC5D x CD3 bispecific antibody claim 2 , wherein the bispecific antibody is IgG4 isotype.
4. The GPRC5D x CD3 bispecific antibody of claim 1 , wherein the antibody binds GPRC5D on the surface of human multiple myeloma cells.
5. An isolated cell expressing the antibody of claim 1 .
6. The cell of claim 5 wherein the cell is a hybridoma.
7. A pharmaceutical composition comprising the GPRC5D x CD3 bispecific antibody of claim 1 and a pharmaceutically acceptable carrier.
8. A method for generating the GPRC5D x CD3 bispecific antibody of claim 1 by culturing the cell of claim 5 .
9. An isolated synthetic polynucleotide encoding the HC1, the HC2, the LC1 or the LC2 of the GPRC5D x CD3 bispecific antibody of claim 1 .