Anti-PVRIG antibodies and methods of use
The present invention is directed to anti-PVRIG antibodies and methods of using same.
1. A method of activating T-cells of a patient with cancer comprising administering an anti-PD-L1 antibody and an anti-PVRIG antibody to said patient, wherein said anti-PVRIG antibody comprises:
i) a heavy chain variable domain comprising the vhCDR1, vhCDR2, and vhCDR3 from SEQ ID NO:1434 and
ii) a light chain variable domain comprising the vlCDR1, vlCDR2, and vlCDR3 from SEQ ID NO:1453,
wherein a subset of said T-cells of said patient are activated.
2. The method according to claim 1 wherein said anti-PVRIG antibody comprises the heavy chain variable domain of SEQ ID NO:1434 and the light chain variable domain of SEQ ID NO:1453.
3. The method according to claim 2 wherein said anti-PVRIG antibody comprises the CH1-hinge-CH2-CH3 region from IgG1, IgG2, IgG3, or IgG4, wherein said hinge region optionally comprises mutations.
4. The method according to claim 3 wherein said anti-PVRIG antibody comprises the CL region of human kappa 2 light chain.
5. The method according to claim 1 wherein said T-cells are cytotoxic T-cells (CTLs).
6. The method according to claim 1 wherein said T-cells are selected from the group consisting of CD4 + T-cells and CD8 + T-cells.
7. 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.
8. A method of activating T-cells of a patient with cancer comprising administering an anti-PD-L1 antibody and an anti-PVRIG antibody to said patient, wherein said anti-PVRIG antibody comprises:
i) a heavy chain variable domain comprising the vhCDR1, vhCDR2, and vhCDR3 from SEQ ID NO:1447 and
ii) a light chain variable domain comprising the vlCDR1, vlCDR2, and vlCDR3 from SEQ ID NO:1462,
wherein a subset of said T-cells of said patient are activated.
9. The method according to claim 8 wherein said anti-PVRIG antibody comprises the heavy chain variable domain of SEQ ID NO:1447 and the light chain variable domain of SEQ ID NO:1462.
10. The method according to claim 9 wherein said anti-PVRIG antibody comprises the CH1-hinge-CH2-CH3 region from IgG1, IgG2, IgG3, or IgG4, wherein said hinge region optionally comprises mutations.
11. The method according to claim 10 wherein said anti-PVRIG antibody comprises the CL region of human kappa 2 light chain.
12. The method according to claim 9 wherein said T-cells are cytotoxic T-cells (CTLs).
13. The method according to claim 9 wherein said T-cells are selected from the group consisting of CD4+ T-cells and CD8+ T-cells.
14. The method according to claim 9 wherein said activation is measured as an increase in interferon-γ production and/or an increase in cytokine secretion.
15. A method of activating T-cells of a patient with cancer comprising administering an anti-PD-L1 antibody and an anti-PVRIG antibody to said patient, wherein said anti-PVRIG antibody comprises:
a) a heavy chain variable domain comprising:
i) a vhCDR1 comprising SEQ ID NO:885;
ii) a vhCDR2 comprising SEQ ID NO:886;
iii) a vhCDR3 comprising SEQ ID NO:887; and
b) a light chain variable domain comprising:
i) a vlCDR1 comprising SEQ ID NO:889;
ii) a vlCDR2 comprising SEQ ID NO:890;
iii) a vlCDR3 comprising SEQ ID NO:891,
wherein a subset of said T-cells of said patient are activated.
16. The method according to claim 15 wherein said anti-PVRIG antibody comprises the CH1-hinge-CH2-CH3 region from IgG1, IgG2, IgG3, or IgG4, wherein said hinge region optionally comprises mutations.
17. The method according to claim 16 wherein said anti-PVRIG antibody comprises the CL region of human kappa 2 light chain.
18. The method according to claim 15 wherein said T-cells are cytotoxic T-cells (CTLs).
19. The method according to claim 15 wherein said T-cells are selected from the group consisting of CD4 + T-cells and CD8 + T-cells.
20. The method according to claim 15 wherein said activation is measured as an increase in interferon-γ production and/or an increase in cytokine secretion.
21. A method of activating T-cells of a patient with cancer comprising administering an anti-PD-L1 antibody and an anti-PVRIG antibody to said patient, wherein said anti-PVRIG antibody comprises:
a) a heavy chain comprising:
i) a VH-CH-hinge-CH2-CH3, wherein the VH is SEQ ID NO:1434 and wherein the CH1-hinge-CH2-CH3 region is from IgG4; and
b) a light chain comprising:
i) a VL-CL, wherein the VL is SEQ ID NO:1453 and wherein the CL region is from human kappa 2 light chain.
22. The method according to claim 21 wherein said hinge region optionally comprises mutations.
23. A method of activating T-cells of a patient with cancer comprising administering an anti-PD-L1 antibody and an anti-PVRIG antibody to said patient, wherein said anti-PVRIG antibody comprises:
a) a heavy chain comprising:
i) a VH-CH1-hinge-CH2-CH3, wherein the VH is SEQ ID NO:1447 and wherein the CH1-hinge-CH2-CH3 region is from IgG4; and
b) a light chain comprising:
i) a VL-CL, wherein the VL is SEQ ID NO:1462 and wherein the CL region is from human kappa 2 light chain.
24. The method according to claim 23 wherein said hinge region optionally comprises mutations.