Anti-TIGIT antibodies
Anti-TIGIT antibodies and antigen binding fragments thereof that inhibit TIGIT-mediated signalling are provided, together with combinations comprising said antibodies or antigen binding fragments thereof and methods for their use.
1. An antibody or antigen binding fragment thereof which binds to human TIGIT, wherein the antibody or antigen binding fragment comprises a combination of HCDR1, HCDR2, HCDR3, LCDR1, LCDR2 and LCDR3, wherein:
HCDR1 comprises SEQ ID NO: 16 (YTFTSYYMH),
HCDR2 comprises SEQ ID NO: 17 (VIGPSGASTSYAQKFQG),
HCDR3 comprises SEQ ID NO: 18 (ARDHSDYWSGIMEV),
LCDR1 comprises SEQ ID NO: 61 (RASQSVRSSYLA),
LCDR2 comprises SEQ ID NO: 62 (GASSRAT), and
LCDR3 comprises SEQ ID NO: 63 (QQYFSPPWT).
2. The antibody or antigen binding fragment according to claim 1 , further comprising a combination of a heavy chain variable domain and a light chain variable domain, wherein the heavy chain variable domain comprises the amino acid sequence shown as SEQ ID NO: 221 or an amino acid sequence at least 95% identical thereto, and the light chain variable domain comprises the amino acid sequence shown as SEQ ID NO: 222 or an amino acid sequence at least 95% identical thereto.
3. The antibody or antigen binding fragment according to claim 1 , further comprising a combination of a heavy chain variable domain and a light chain variable domain, wherein the heavy chain variable domain comprises the amino acid sequence shown as SEQ ID NO: 219 or an amino acid sequence at least 95% identical thereto, and the light chain variable domain comprises the amino acid sequence shown as SEQ ID NO: 220 or an amino acid sequence at least 95% identical thereto.
4. The antibody or antigen binding fragment according to claim 1 , wherein the antibody or antigen binding fragment comprises a fragment of a human immunoglobulin.
5. The antibody or antigen binding fragment according to claim 4 , wherein the fragment of a human immunoglobulin is a fragment of human IgG.
6. The antibody or antigen binding fragment according to claim 1 , wherein the antibody is a human IgG1 antibody.
7. The antibody or antigen binding fragment according to claim 1 , wherein the antibody or antigen binding fragment selectively depletes TIGIT-expressing Treg cells.
8. The antibody or antigen binding fragment according to claim 1 , wherein the antibody or antigen binding fragment decreases expression of TIGIT on CD8 T cells and/or on Treg cells.
9. A pharmaceutical composition comprising: i) an effective amount of an antibody or antigen binding fragment thereof, wherein the antibody or antigen binding fragment binds to human TIGIT, wherein the antibody or antigen binding fragment comprises a combination of HCDR1, HCDR2, HCDR3, LCDR1, LCDR2 and LCDR3, wherein:
HCDR1 comprises SEQ ID NO: 16 (YTFTSYYMH),
HCDR2 comprises SEQ ID NO: 17 (VIGPSGASTSYAQKFQG),
HCDR3 comprises SEQ ID NO: 18 (ARDHSDYWSGIMEV),
LCDR1 comprises SEQ ID NO: 61 (RASQSVRSSYLA),
LCDR2 comprises SEQ ID NO: 62 (GASSRAT),
LCDR3 comprises SEQ ID NO: 63 (QQYFSPPWT); and
ii) a pharmaceutically acceptable carrier.
10. The pharmaceutical composition of claim 9 , wherein the antibody or antigen binding fragment comprises a combination of a heavy chain variable domain and a light chain variable domain, wherein the heavy chain variable domain comprises the amino acid sequence shown as SEQ ID NO: 221 or an amino acid sequence at least 95% identical thereto, and the light chain variable domain comprises the amino acid sequence shown as SEQ ID NO: 222 or an amino acid sequence at least 95% identical thereto.
11. The pharmaceutical composition of claim 9 , wherein the antibody or antigen binding fragment comprises a combination of a heavy chain variable domain and a light chain variable domain, wherein the heavy chain variable domain comprises the amino acid sequence shown as SEQ ID NO: 219 or an amino acid sequence at least 95% identical thereto, and the light chain variable domain comprises the amino acid sequence shown as SEQ ID NO: 220 or an amino acid sequence at least 95% identical thereto.
12. The pharmaceutical composition of claim 9 , wherein the antibody or antigen binding fragment comprises a fragment of a human immunoglobulin.
13. The pharmaceutical composition of claim 12 , wherein the antibody or antigen binding fragment comprises a fragment of human IgG.
14. The pharmaceutical composition of claim 13 , wherein the antibody is a human IgG1 antibody.
15. The pharmaceutical composition of claim 9 , wherein the antibody or antigen binding fragment selectively depletes TIGIT-expressing Treg cells.
16. The pharmaceutical composition of claim 9 , wherein the antibody or antigen binding fragment decreases expression of TIGIT on CD8 T cells and/or on Treg cells.
17. A method of treating cancer in a subject comprising administering an effective amount of an antibody or antigen-binding fragment according to claim 1 to the subject, thereby treating the cancer.
18. The method of treating cancer according to claim 17 , further comprising administering a second effective amount of a second therapeutic agent.
19. A method of treating cancer according to claim 18 , wherein the second therapeutic agent is selected from the group consisting of: a chemotherapeutic agent, an anti-PD1 antibody, an anti-PD-L1 antibody, an anti-41BB antibody, an anti-OX40 antibody, an anti-GITR antibody, and an anti-ICOS antibody.
20. The antibody or antigen binding fragment according to claim 2 , wherein the heavy chain variable domain comprises the amino acid sequence shown as SEQ ID NO: 221 and the light chain variable domain comprises the amino acid sequence shown as SEQ ID NO: 222.
21. The antibody or antigen binding fragment according to claim 3 , wherein the heavy chain variable domain comprises the amino acid sequence shown as SEQ ID NO: 219 and the light chain variable domain comprises the amino acid sequence shown as SEQ ID NO: 220.
22. The antibody or antigen binding fragment according to claim 20 or 21 , wherein the antibody is a human IgG1 antibody.
23. A pharmaceutical composition comprising an effective amount of the antibody or antigen binding fragment according to claim 20 or 21 , and a pharmaceutically acceptable carrier.
24. A method of treating cancer in a subject comprising administering an effective amount of the antibody or antigen-binding fragment according to claim 20 or 21 to the subject, thereby treating the cancer.
25. The method of treating cancer according to claim 24 , further comprising administering a second effective amount of a second therapeutic agent.
26. The method of treating cancer according to claim 25 , wherein the second therapeutic agent is selected from the group consisting of: a chemotherapeutic agent, an anti-PD1 antibody, an anti-PD-L1 antibody, an anti-41BB antibody, an anti-OX40 antibody, an anti-GITR antibody, and an anti-ICOS antibody.