Anti-GITR antibodies and uses thereof
Provided herein are antibodies, and antigen-binding fragments thereof that specifically bind glucocorticoid-induced tumor necrosis factor receptor (GITR), compositions comprising the antibodies or antigen-binding fragments thereof, and methods of using the same, including, e.g., methods of treatment using the same.
1. An isolated antibody or antigen-binding fragment thereof that binds glucocorticoid-induced tumor necrosis factor receptor (GITR), wherein
the antibody or antigen-binding fragment thereof comprises: (i) three heavy chain complementarity determining regions (HCDR1, HCDR2, and HCDR3), wherein the HCDR1 comprises the amino acid sequence of SEQ ID NO:4, the HCDR2 comprises the amino acid sequence of SEQ ID NO:6, and the HCDR3 comprises an amino acid sequence selected from the group consisting of SEQ ID NO:24, SEQ ID NO:30, SEQ ID NO:36, and SEQ ID NO:42; and (ii) three light chain complementarity determining regions (LCDR1, LCDR2, and LCDR3), wherein the LCDR1 comprises the amino acid sequence of SEQ ID NO:12, the LCDR2 comprises the amino acid sequence of SEQ ID NO:14, and the LCDR3 comprises the amino acid sequence of SEQ ID NO:16.
2. The isolated antibody or antigen-binding fragment thereof of claim 1 comprising an LCVR having the amino acid sequence of SEQ ID NO: 10.
3. The isolated antibody or antigen-binding fragment thereof of claim 1 , wherein the antibody or antigen-binding fragment comprises a HCDR1 comprising an amino acid sequence of SEQ ID NO: 4, HCDR2 comprising an amino acid sequence of SEQ ID NO: 6, HCDR3 comprising an amino acid sequence of SEQ ID NO: 24, LCDR1 comprising an amino acid sequence of SEQ ID NO: 12, LCDR2 comprising an amino acid sequence of SEQ ID NO: 14, and LCDR3 comprising an amino acid sequence of SEQ ID NO: 16.
4. The isolated antibody or antigen-binding fragment thereof of claim 1 , wherein the antibody or antigen-binding fragment comprises a HCDR1 comprising an amino acid sequence of SEQ ID NO: 4, HCDR2 comprising an amino acid sequence of SEQ ID NO: 6, HCDR3 comprising an amino acid sequence of SEQ ID NO: 30, LCDR1 comprising an amino acid sequence of SEQ ID NO: 12, LCDR2 comprising an amino acid sequence of SEQ ID NO: 14, and LCDR3 comprising an amino acid sequence of SEQ ID NO: 16.
5. The isolated antibody or antigen-binding fragment thereof of claim 1 , wherein the antibody or antigen-binding fragment comprises a HCDR1 comprising an amino acid sequence of SEQ ID NO: 4, HCDR2 comprising an amino acid sequence of SEQ ID NO: 6, HCDR3 comprising an amino acid sequence of SEQ ID NO: 36, LCDR1 comprising an amino acid sequence of SEQ ID NO: 12, LCDR2 comprising an amino acid sequence of SEQ ID NO: 14, and LCDR3 comprising an amino acid sequence of SEQ ID NO: 16.
6. The isolated antibody or antigen-binding fragment thereof claim 1 , wherein the antibody or antigen-binding fragment comprises a HCDR1 comprising an amino acid sequence of SEQ ID NO: 4, HCDR2 comprising an amino acid sequence of SEQ ID NO: 6, HCDR3 comprising an amino acid sequence of SEQ ID NO: 42, LCDR1 comprising an amino acid sequence of SEQ ID NO: 12, LCDR2 comprising an amino acid sequence of SEQ ID NO: 14, and LCDR3 comprising an amino acid sequence of SEQ ID NO: 16.
7. The isolated antibody or antigen-binding fragment thereof of claim 3 comprising an HCVR having the amino acid sequence of SEQ ID NO: 22.
8. The isolated antibody or antigen-binding fragment thereof of claim 4 comprising an HCVR having the amino acid sequence of SEQ ID NO: 28.
9. The isolated antibody or antigen-binding fragment thereof of claim 5 comprising an HCVR having the amino acid sequence of SEQ ID NO: 34.
10. The isolated antibody or antigen-binding fragment thereof of claim 6 comprising an HCVR having the amino acid sequence of SEQ ID NO: 40.
11. The isolated antibody or antigen-binding fragment thereof of claim 1 , wherein the antibody or antigen-binding fragment thereof comprises an HCVR comprising an amino acid sequence of SEQ ID NO: 22, and an LCVR comprising an amino acid sequence of SEQ ID NO: 10.
12. The isolated antibody or antigen-binding fragment thereof of claim 1 , wherein the antibody or antigen-binding fragment thereof comprises an HCVR comprising an amino acid sequence of SEQ ID NO: 28, and an LCVR comprising an amino acid sequence of SEQ ID NO: 10.
13. The isolated antibody or antigen-binding fragment thereof of claim 1 , wherein the antibody or antigen-binding fragment thereof comprises an HCVR comprising an amino acid sequence of SEQ ID NO: 34, and an LCVR comprising an amino acid sequence of SEQ ID NO: 10.
14. The isolated antibody or antigen-binding fragment thereof of claim 1 , wherein the antibody or antigen-binding fragment thereof comprises an HCVR comprising an amino acid sequence of SEQ ID NO: 40, and an LCVR comprising an amino acid sequence of SEQ ID NO: 10.
15. The isolated antibody or antigen-binding fragment thereof of claim 1 comprising a heavy chain and a light chain, wherein the heavy chain comprises an amino acid sequence of SEQ ID NO: 26.
16. The isolated antibody or antigen-binding fragment thereof of claim 1 comprising a heavy chain and a light chain, wherein the heavy chain comprises an amino acid sequence of SEQ ID NO: 32.
17. The isolated antibody or antigen-binding fragment thereof of claim 1 comprising a heavy chain and a light chain, wherein the heavy chain comprises an amino acid sequence of SEQ ID NO: 38.
18. The isolated antibody or antigen-binding fragment thereof of claim 1 comprising a heavy chain and a light chain, wherein the heavy chain comprises an amino acid sequence of SEQ ID NO: 44.
19. The isolated antibody or antigen-binding fragment thereof of claim 1 , comprising a heavy chain and a light chain, wherein the light chain comprises an amino acid sequence of SEQ ID NO: 20.
20. A pharmaceutical composition comprising the antibody or antigen-binding fragment thereof of claim 1 and a pharmaceutically acceptable carrier or diluent.
21. An isolated polynucleotide molecule comprising a polynucleotide sequence that encodes an HCVR and optionally an LCVR of an antibody of claim 1 .
22. An isolated polynucleotide molecule comprising a polynucleotide sequence that encodes a heavy chain and optionally a light chain of an antibody as set forth in claim 21 .
23. A vector comprising the polynucleotide sequence of claim 21 .
24. An isolated host cell expressing the vector of claim 23 .