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. A method for treating cancer, the method comprising administering to a human patient in need thereof an effective amount of a pharmaceutical composition comprising a pharmaceutically acceptable carrier and an isolated antibody or antigen binding fragment thereof which binds to a human T cell Immunoreceptor with Ig and ITIM domains (TIGIT), wherein the antibody or antigen binding fragment comprises a heavy chain variable domain (VH) comprising a HCDR1, a HCDR2, and a HCDR3, and a light chain variable domain (VL) comprising a LCDR1, a LCDR2 and a LCDR3, wherein:
the LCDR1 comprises SEQ ID NO: 61, the LCDR2 comprises SEQ ID NO:62, and the LCDR3 comprises SEQ ID NO:63; and
the HCDR1 comprises SEQ ID NO: 16, the HCDR2 comprises SEQ ID NO:17, and the HCDR3 comprises SEQ ID NO:18.
2. The method according to claim 1 , wherein the VH comprises an amino acid sequence with at least 95%, 97%, 98% or 99% sequence identity to SEQ ID NO:221 wherein all differences are located in a framework region of the VH; and the VL comprises an amino acid sequence with at least 95%, 97%, 98% or 99% sequence identity to SEQ ID NO:222 wherein all differences are located in a framework region of the VL.
3. The method according to claim 1 , wherein the VH comprises SEQ ID NO:221 and the VL comprises SEQ ID NO:222.
4. The method according to claim 1 , wherein the antibody is a human IgG antibody.
5. The method according to claim 1 , wherein the antibody is a human IgG1 antibody.
6. The method according to claim 1 , wherein the effective amount of the pharmaceutical composition is effective for selective depletion of TIGIT-expressing T-regulatory (T-reg) cells in the subject.
7. The method of claim 1 , wherein the cancer is a lung cancer.
8. A method for increasing patient survival in a human patient in need of depletion of T reg cells, the method comprising administering to the human patient an effective amount of a pharmaceutical composition comprising a pharmaceutically acceptable carrier and an isolated antibody or antigen binding fragment thereof which binds to a human T cell Immunoreceptor with Ig and ITIM domains (TIGIT), wherein the antibody or antigen binding fragment comprises a heavy chain variable domain (VH) comprising a HCDR1, a HCDR2, and a HCDR3, and a light chain variable domain (VL) comprising a LCDR1, a LCDR2 and a LCDR3, wherein:
the LCDR1 comprises SEQ ID NO: 61, the LCDR2 comprises SEQ ID NO:62, and the LCDR3 comprises SEQ ID NO:63; and
the HCDR1 comprises SEQ ID NO: 16, the HCDR2 comprises SEQ ID NO:17, and the HCDR3 comprises SEQ ID NO:18.
9. The method according to claim 8 , wherein the VH comprises SEQ ID NO:221 and the VL comprises SEQ ID NO:222.
10. A method for decreasing tumor volume, the method comprising administering to a human patient in need thereof an effective amount of a pharmaceutical composition comprising a pharmaceutically acceptable carrier and an isolated antibody or antigen binding fragment thereof which binds to a human T cell Immunoreceptor with Ig and ITIM domains (TIGIT), wherein the antibody or antigen binding fragment comprises a heavy chain variable domain (VH) comprising a HCDR1, a HCDR2, and a HCDR3, and a light chain variable domain (VL) comprising a LCDR1, a LCDR2 and a LCDR3, wherein:
the LCDR1 comprises SEQ ID NO: 61, the LCDR2 comprises SEQ ID NO:62, and the LCDR3 comprises SEQ ID NO:63; and
the HCDR1 comprises SEQ ID NO: 16, the HCDR2 comprises SEQ ID NO:17, and the HCDR3 comprises SEQ ID NO:18.
11. The method according to claim 10 , wherein the VH comprises SEQ ID NO:221 and the VL comprises SEQ ID NO:222.
12. The method according to claim 8 , wherein the antibody is a human IgG1 antibody.
13. The method according to claim 8 , wherein the human patient has lung cancer.
14. The method according to claim 10 , wherein the antibody is a human IgG1 antibody.
15. The method according to claim 10 , wherein the human patient has lung cancer.