Antibodies specific to delta 1 chain of T cell receptor
Disclosed herein are antibodies specific to a delta1 chain of a γδ T cell receptor and methods of using such for modulating γδ T cell bioactivity. Such anti-Delta1 antibodies may also be used to treat diseases associated with γδ T cell activation, such as solid tumors, or for detecting presence of γδ1 T cells.
1. An isolated antibody, which binds to delta1 chain of human T cell receptor, wherein the antibody comprises (a) a heavy chain variable region (V H ), which comprises a heavy chain complementarity determining region 1 (VHCDR1) set forth as SEQ ID NO: 43, a heavy chain complementary determining region 2 (VHCDR2) set forth as SEQ ID NO: 57, and a heavy chain complementary determining region 3 (VHCDR3) set forth as SEQ ID NO: 77; and a light chain variable region (VL), which comprises a light chain complementarity determining region 1 (VLCDR1) set forth as SEQ ID NO: 46, a light chain complementary determining region 2 (VLCDR2) set forth as SEQ ID NO: 47, and a light chain complementary determining region 3 (VLCDR3) set forth as SEQ ID NO: 78.
2. The isolated antibody of claim 1 , wherein the the V H is set forth as SEQ ID NO: 23 and the V L is set forth as SEQ ID NO: 24.
3. The isolated antibody of claim 1 , wherein the antibody comprises a heavy chain constant region set forth as SEQ ID NO: 31, and/or wherein the antibody comprises a light chain constant region set forth as SEQ ID NO: 79.
4. The isolated antibody of claim 2 , wherein the antibody comprises a heavy chain constant region set forth as SEQ ID NO: 31, and/or wherein the antibody comprises a light chain constant region set forth as SEQ ID NO: 79.
5. The isolated antibody of claim 2 , wherein the antibody comprises a heavy chain (HC) set forth as SEQ ID NO: 84 and a light chain (LC) set forth as SEQ ID NO: 83.
6. The isolated antibody of claim 1 , wherein the antibody is a full-length antibody or an antigen-binding fragment thereof.
7. The isolated antibody of claim 1 , wherein the antibody is a single chain antibody.
8. The isolated antibody of claim 1 , wherein the antibody is a human antibody or a humanized antibody.
9. The isolated antibody of claim 1 , wherein the antibody is an IgG molecule.
10. The isolated antibody of claim 9 , wherein the IgG molecule is IgG1 or IgG4.
11. The isolated antibody of claim 10 , wherein the IgG molecule is an IgG1 molecule.
12. The isolated antibody of claim 1 , wherein the antibody has a VHCDR1 set forth as SEQ ID NO: 43, a VHCDR2 set forth as SEQ ID NO: 57, a VHCDR3 set forth as SEQ ID NO: 77, a VLCDR1 set forth as SEQ ID NO: 46, a VLCDR2 set forth as SEQ ID NO: 47, a VLCDR3 set forth as SEQ ID NO: 78, and has a heavy chain constant region set forth as SEQ ID NO: 31 and a light chain constant region set forth as SEQ ID NO: 79.
13. The isolated antibody of claim 2 , wherein the antibody is a full-length antibody or an antigen-binding fragment thereof.
14. The isolated antibody of claim 2 , wherein the antibody is a single chain antibody.
15. The isolated antibody of claim 2 , wherein the antibody is a human antibody or a humanized antibody.
16. The isolated antibody of claim 2 , wherein the antibody is an IgG molecule.
17. The isolated antibody of claim 16 , wherein the IgG molecule is IgG1 or IgG4.
18. The isolated antibody of claim 17 , wherein the IgG molecule is an IgG1 molecule.
19. The isolated antibody of claim 1 , wherein the antibody is capable of binding to γδ1 TCRs containing two or more gamma chains selected from 3, 4, 5, 8, and/or 9.
20. The isolated antibody of claim 1 , wherein the antibody inhibits the activation of γδ T cells in a subject.
21. A pharmaceutical composition comprising the antibody of claim 13 and a pharmaceutically acceptable carrier.
22. A pharmaceutical composition comprising the antibody of claim 1 and a pharmaceutically acceptable carrier.
23. A pharmaceutical composition comprising the antibody of claim 2 and a pharmaceutically acceptable carrier.
24. A pharmaceutical composition comprising the antibody of claim 5 and a pharmaceutically acceptable carrier.
25. The antibody of claim 1 , wherein the V H comprises an amino acid sequence at least 85% identical to SEQ ID NO: 23 and wherein the V L comprises an amino acid sequence at least 85% identical to SEQ ID NO: 24.
26. The antibody of claim 1 , wherein the V H comprises an amino acid sequence at least 90% identical to SEQ ID NO: 23 and wherein the V L comprises an amino acid sequence at least 90% identical to SEQ ID NO: 24.