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-PVRIG antibody to said patient, wherein said anti-PVRIG antibody comprises:
a) the vhCDR1, vhCDR2, and vhCDR3 from SEQ ID NO:1434 and
b) the vlCDR1, vlCDR2, and vlCDR3 from SEQ ID NO:1453,
wherein said CDRs comprise from 0 to 4 substitutions and wherein no individual CDR comprises more than 1 substitution, and wherein the vhCDR3 and vlCDR3 comprise no substitutions, and
wherein a subset of said T-cells of said patient are activated.
2. A method according to claim 1 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.
3. A method according to claim 1 wherein said anti-PVRIG antibody comprises the CL region of human kappa 2 light chain.
4. A method according to claim 1 wherein said T-cells are cytotoxic T-cells (CTLs).
5. A method according to claim 1 wherein said T-cells are selected from the group consisting of CD4+ T-cells and CD8+ T-cells.
6. A method according to claim 1 wherein said activation is measured as an increase in interferon-γ production and/or an increase in cytokine secretion.
7. A method of activating T-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 a sequence exhibiting at least 90% identity to SEQ ID NO:1434, wherein each individual vhCDR from SEQ ID NO:1434 comprises no more than 1 substitution, and wherein the vhCDR3 comprises no substitutions, and
ii) a light chain variable domain comprising a sequence exhibiting at least 90% identity to SEQ ID NO:1453, wherein each individual v1CDR from SEQ ID NO:1453 comprises no more than 1 substitution, and wherein the vlCDR3 comprises no substitutions, and
wherein a subset of said T-cells of said patient are activated.
8. A method according to claim 7 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.
9. A method according to claim 7 wherein said anti-PVRIG antibody comprises the CL region of human kappa 2 light chain.
10. A method according to claim 7 wherein said T-cells are cytotoxic T-cells (CTLs).
11. A method according to claim 7 wherein said T-cells are selected from the group consisting of CD4+ T-cells and CD8+ T-cells.
12. A method according to claim 7 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 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 wherein said heavy chain variable domain comprises a sequence exhibiting at least 90% identity to SEQ ID NO:1434, wherein each individual vhCDR from SEQ ID NO:1434 comprises no more than 1 substitution, and wherein the vhCDR3 comprises no substitutions, and
ii) a light chain variable domain comprising the vlCDR1, vlCDR2, and vlCDR3 from SEQ ID NO:1453 and wherein said light chain variable domain comprises a sequence exhibiting at least 90% identity to SEQ ID NO:1453, wherein each individual vlCDR from SEQ ID NO:1453 comprises no more than 1 substitution, and wherein the vlCDR3 comprises no substitutions, and
wherein a subset of said T-cells of said patient are activated.
14. A method according to claim 13 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.
15. A method according to claim 13 wherein said anti-PVRIG antibody comprises the CL region of human kappa 2 light chain.
16. A method according to claim 13 wherein said T-cells are cytotoxic T-cells (CTLs).
17. A method according to claim 13 wherein said T-cells are selected from the group consisting of CD4+ T-cells and CD8+ T-cells.
18. A method according to claim 13 wherein said activation is measured as an increase in interferon-γ production and/or an increase in cytokine secretion.
19. A method of activating T-cells of a patient with cancer comprising administering an anti-PVRIG antibody to said patient, wherein said anti-PVRIG antibody comprises:
a) the vhCDR1, vhCDR2, and vhCDR3 from SEQ ID NO:1447 and
b) the vlCDR1, vlCDR2, and vlCDR3 from SEQ ID NO:1462,
wherein said CDRs comprise from 0 to 4 substitutions, and no said CDR comprises more than 1 substitution, and wherein the vhCDR3 and vlCDR3 comprise no substitutions, and
wherein a subset of said T-cells of said patient are activated.
20. A method according to claim 19 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.
21. A method according to claim 19 wherein said anti-PVRIG antibody comprises the CL region of human kappa 2 light chain.
22. A method according to claim 19 wherein said T-cells are cytotoxic T-cells (CTLs).
23. A method according to claim 19 wherein said T-cells are selected from the group consisting of CD4+ T-cells and CD8+ T-cells.
24. A method according to claim 19 wherein said activation is measured as an increase in interferon-γ production and/or an increase in cytokine secretion.
25. A method of activating T-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 a sequence exhibiting at least 90% identity to SEQ ID NO:1447, wherein each individual vhCDR from SEQ ID NO:1447 comprises no more than 1 substitution, and wherein the vhCDR3 comprises no substitutions, and
ii) a light chain variable domain comprising a sequence exhibiting at least 90% identity to SEQ ID NO:1462, wherein each individual vlCDR from SEQ ID NO:1462 comprises no more than 1 substitution, and wherein the vlCDR3 comprises no substitutions, and
wherein a subset of said T-cells of said patient are activated.
26. A method according to claim 25 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.
27. A method according to claim 25 wherein said anti-PVRIG antibody comprises the CL region of human kappa 2 light chain.
28. A method according to claim 25 wherein said T-cells are cytotoxic T-cells (CTLs).
29. A method according to claim 25 wherein said T-cells are selected from the group consisting of CD4+ T-cells and CD8+ T-cells.
30. A method according to claim 25 wherein said activation is measured as an increase in interferon-γ production and/or an increase in cytokine secretion.
31. A method of activating T-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 wherein said heavy chain variable domain comprises a sequence exhibiting at least 90% identity to SEQ ID NO:1447, wherein each individual vhCDR from SEQ ID NO:1447 comprises no more than 1 substitution, and wherein the vhCDR3 comprises no substitutions, and
ii) a light chain variable domain comprising the vlCDR1, vlCDR2, and vlCDR3 from SEQ ID NO:1462 and wherein said light chain variable domain comprises a sequence exhibiting at least 90% identity to SEQ ID NO:1462, wherein each individual vlCDR from SEQ ID NO:1462 comprises no more than 1 substitution, and wherein the vlCDR3 comprises no substitutions, and
wherein a subset of said T-cells of said patient are activated.
32. A method according to claim 31 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.
33. A method according to claim 31 wherein said anti-PVRIG antibody comprises the CL region of human kappa 2 light chain.
34. A method according to claim 31 wherein said T-cells are cytotoxic T-cells (CTLs).
35. A method according to claim 31 wherein said T-cells are selected from the group consisting of CD4+ T-cells and CD8+ T-cells.
36. A method according to claim 31 wherein said activation is measured as an increase in interferon-γ production and/or an increase in cytokine secretion.
37. A method of activating T-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 variable domain comprising:
i) a vhCDR1 selected from the group consisting of SEQ ID NO:885 or a SEQ ID NO:885 variant comprising 1 amino acid substitution;
ii) a vhCDR2 selected from the group consisting of SEQ ID NO:886 or a SEQ ID NO:886 variant comprising 1 amino acid substitution;
iii) a vhCDR3 has the sequence of SEQ ID NO:887; and
b) a light chain variable domain comprising:
i) a vlCDR1 selected from the group consisting of SEQ ID NO:889 or a SEQ ID NO:889 variant comprising 1 amino acid substitution;
ii) a vlCDR2 selected from the group consisting of SEQ ID NO:890 or a SEQ ID NO:890 variant comprising 1 amino acid substitution;
iii) a vlCDR3 has the sequence of SEQ ID NO:891, and
wherein a subset of said T-cells of said patient are activated.
38. A method according to claim 37 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.
39. A method according to claim 37 wherein said anti-PVRIG antibody comprises the CL region of human kappa 2 light chain.
40. A method according to claim 37 wherein said T-cells are cytotoxic T-cells (CTLs).
41. A method according to claim 37 wherein said T-cells are selected from the group consisting of CD4+ T-cells and CD8+ T-cells.
42. A method according to claim 37 wherein said activation is measured as an increase in interferon-γ production and/or an increase in cytokine secretion.