Anti-TIGIT antibodies, anti-PVRIG antibodies and combinations thereof
Anti-PVRIG and anti-TIGIT antibodies are provided.
1. A method of activating T-cells of a patient with cancer comprising administering an antigen binding domain that binds to human TIGIT (SEQ ID NO:97) to said patient, wherein said antigen binding domain comprises:
a) a variable heavy domain comprising SEQ ID NO:160; and
b) a variable light domain comprising SEQ ID NO:165.
2. The method according to claim 1 wherein said antigen binding domain is an antibody, and wherein said antibody comprises:
a) a heavy chain comprising VH-CH1-hinge-CH2-CH3, wherein said VH comprises SEQ ID NO:160; and
b) a light chain comprising VL-VC, wherein said VL comprising SEQ ID NO:165 and VC is either kappa or lambda.
3. The method according to claim 2 wherein the sequence of said CH1-hinge-CH2-CH3 is selected from human IgG1, IgG2 and IgG4, and variants thereof.
4. The method according to claim 2 wherein said heavy chain has SEQ ID NO:164 and said light chain has SEQ ID NO:169.
5. The method according to claim 2 further comprising administering a second antibody that binds to a human checkpoint receptor protein.
6. The method according to claim 5 wherein said second antibody binds human PD-1.
7. The method according to claim 5 wherein said second antibody binds human PVRIG extracellular domain (ECD) (SEQ ID NO:80).
8. The method according to claim 7 wherein said second antibody comprises an antigen binding domain comprising a variable heavy domain comprising SEQ ID NO:5 and a variable light domain comprising SEQ ID NO:10.
9. The method according to claim 7 wherein the heavy chain of said second antibody has SEQ ID NO:9 and the light chain of said second antibody has SEQ ID NO:14.
10. The method according to claim 1 wherein said T-cells are cytotoxic T-cells (CTLs).
11. The method according to claim 1 wherein said T-cells are selected from the group consisting of CD4 + T-cells and CD8 + T-cells.
12. The method according to claim 1 wherein said activation is measured as an increase in interferon-γ production and/or an increase in cytokine secretion.
13. A method of activating T-cells of a patient with cancer comprising administering an antigen binding domain that binds to human TIGIT (SEQ ID NO:97) to said patient, wherein said antigen binding domain comprises:
a) a variable heavy domain comprising SEQ ID NO:150; and
b) a variable light domain comprising SEQ ID NO:155.
14. The method according to claim 13 wherein said antigen binding domain is an antibody, and wherein said antibody comprises:
a) a heavy chain comprising VH-CH1-hinge-CH2-CH3, wherein said VH comprises SEQ ID NO:150; and
b) a light chain comprising VL-VC, wherein said VL comprising SEQ ID NO:155 and VC is either kappa or lambda.
15. The method according to claim 14 wherein the sequence of said CH1-hinge-CH2-CH3 is selected from human IgG1, IgG2 and IgG4, and variants thereof.
16. The method according to claim 14 wherein said heavy chain has SEQ ID NO:154 and said light chain has SEQ ID NO:159.
17. The method according to claim 14 further comprising administering a second antibody that binds to a human checkpoint receptor protein.
18. The method according to claim 17 wherein said second antibody binds human PD-1.
19. The method according to claim 17 wherein said second antibody binds human PVRIG extracellular domain (ECD) (SEQ ID NO:80).
20. The method according to claim 19 wherein said second antibody comprises an antigen binding domain comprising a variable heavy domain comprising SEQ ID NO:5 and a variable light domain comprising SEQ ID NO:10.