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 NK-cells of a patient with cancer comprising administering 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 NK-cells of said patient are activated.
2. A 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. A 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. A method according to claim 3 wherein said anti-PVRIG antibody comprises the CL region of human kappa 2 light chain.
5. A method according to claim 1 wherein said NK-cells are CD16+ lymphocytes.
6. A method according to claim 1 wherein said NK-cells are CD56+ NK cells.
7. A method according to claim 1 wherein said activation is measured as an increase in expression of one or more activation makers.
8. A method according to claim 7 wherein said activation markers are selected from the group consisting of CD107a, CD137, CD69, granzyme, and perforin.
9. A method according to claim 1 wherein said activation is measured as an increase in proliferation of said NK-cells.
10. A method according to claim 1 wherein said activation is measured as an increase in secretion of one or more cytokines.
11. A method according to claim 10 wherein said one or more cytokines is selected from the group consisting of IFNγ and TNF.
12. A method according to claim 1 wherein said activation is measured as an increase in direct killing of target cells.
13. A method of activating NK-cells of a patient with cancer comprising administering 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 NK-cells of said patient are activated.
14. A method according to claim 13 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.
15. A method according to claim 14 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.
16. A method according to claim 15 wherein said anti-PVRIG antibody comprises the CL region of human kappa 2 light chain.
17. A method according to claim 13 wherein said activation markers are selected from the group consisting of CD107a, CD137, CD69, granzyme, and perforin.
18. A method according to claim 13 wherein said activation is measured as an increase in proliferation of said NK-cells.
19. A method according to claim 13 wherein said activation is measured as an increase in secretion of one or more cytokines.
20. A method according to claim 19 , wherein said one or more cytokines is selected from the group consisting of IFNγ and TNF.
21. A method according to claim 13 wherein said activation is measured as an increase in direct killing of target cells.
22. A method of activating NK-cells of a patient with cancer comprising administering an anti-PD-1 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.
23. A method according to claim 22 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.
24. A method according to claim 23 wherein said anti-PVRIG antibody comprises the CL region of human kappa 2 light chain.
25. A method according to claim 22 wherein said activation markers are selected from the group consisting of CD107a, CD137, CD69, granzyme, and perforin.
26. A method according to claim 22 wherein said activation is measured as an increase in proliferation of said NK-cells.
27. A method according to claim 22 wherein said activation is measured as an increase in secretion of one or more cytokines.
28. A method according to claim 27 , wherein said one or more cytokines is selected from the group consisting of IFNγ and TNF.
29. A method according to claim 22 wherein said activation is measured as an increase in direct killing of target cells.
30. A method of activating NK-cells of a patient with cancer comprising administering 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: 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.
31. A method according to claim 30 wherein said hinge region optionally comprises mutations.
32. A method of activating NK-cells of a patient with cancer comprising administering an anti-PD-1 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.
33. A method according to claim 32 wherein said hinge region optionally comprises mutations.