Anti-CD112R compositions and methods

1. A method of treating a cancer in a subject in need thereof, the method comprising administering to the subject a therapeutically effective amount of an antibody or antigen binding portion thereof that binds to CD112R and comprises:

i) a heavy chain variable region CDR1 comprising the amino acid sequence of SEQ ID NO: 701;

ii) a heavy chain variable region CDR2 comprising the amino acid sequence of SEQ ID NO: 702;

iii) a heavy chain variable region CDR3 comprising the amino acid sequence of SEQ ID NO: 703;

iv) a light chain variable region CDR1 comprising the amino acid sequence of SEQ ID NO: 704;

v) a light chain variable region CDR2 comprising the amino acid sequence of SEQ ID NO: 705; and

vi) a light chain variable region CDR3 comprising the amino acid sequence of SEQ ID NO: 706.

2. The method of claim 1 , wherein the antibody or antigen binding portion thereof comprises a heavy chain variable region having a sequence at least 90% identical to the amino acid sequence of SEQ ID NO: 712 and a light chain variable region having a sequence at least 90% identical to the amino acid sequence of SEQ ID NO: 718.

3. The method of claim 2 , wherein the antibody or antigen binding portion thereof comprises a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 712 and a light chain variable region comprising the amino acid sequence of SEQ ID NO: 718.

4. The method of claim 3 , wherein the antibody is a monoclonal antibody.

5. The method of claim 3 , wherein the antibody is fully human or humanized.

6. The method of claim 3 , wherein the Fc region of the antibody comprises IgG1, IgG2, IgG3, or IgG4.

7. The method of claim 6 , wherein the antibody comprises a human IgG1 heavy chain constant region.

8. The method of claim 6 , wherein the antibody comprises a human IgG4 heavy chain constant region.

9. The method of claim 8 , wherein the antibody comprises a mutant human IgG4 heavy chain constant region.

10. The method of claim 9 , wherein the mutant IgG4 heavy chain constant region comprises a mutation selected from a substitution at Ser228, a substitution at Leu235, a substitution at Asn297, or a combination thereof, numbering according to EU numbering.

11. The method of claim 10 , wherein the mutant IgG4 heavy chain constant region comprises an S228P substitution and an L235E substitution, numbering according to EU numbering.

12. The method of claim 1 , wherein the CD112R is a human CD112R.

13. The method of claim 1 , wherein the subject is a human subject.

14. The method of claim 13 , wherein the cancer is carcinoma, lymphoma, blastoma, sarcoma, or leukemia.

15. The method of claim 13 , wherein the cancer is squamous cell cancer, small-cell lung cancer, pituitary cancer, esophageal cancer, astrocytoma, soft tissue sarcoma, non-small cell lung cancer, adenocarcinoma of the lung, squamous carcinoma of the lung, cancer of the peritoneum, hepatocellular cancer, gastrointestinal cancer, pancreatic cancer, glioblastoma, cervical cancer, ovarian cancer, liver cancer, bladder cancer, hepatoma, breast cancer, colon cancer, colorectal cancer, endometrial or uterine carcinoma, salivary gland carcinoma, kidney cancer, renal cell carcinoma, liver cancer, prostate cancer, vulval cancer, thyroid cancer, hepatic carcinoma, brain cancer, endometrial cancer, testis cancer, cholangiocarcinoma, gallbladder carcinoma, gastric cancer, melanoma, or various types of head and neck cancer.

16. The method of claim 1 , further comprising administering to the subject:

i) an antagonist of PD-1, PD-L1, CTLA-4, Lag-3, TIM-3, TIGIT, CD96, PVRL1, PVRL2, PVRL3, PVRL4, CD155, CD47, CD39 or IL-27;

ii) a STING agonist; or

iii) a combination of (i) and (ii).

17. The method of claim 1 , further comprising administering to the subject an antagonist of TIGIT, an antagonist of CD96, an antagonist of PD-1 or an antagonist of PD-L1.

18. The method of claim 1 , further comprising administering to the subject a radiotherapy or surgery.

19. The method of claim 1 , further comprising administering to the subject chemotherapy, an opsonizing agent, or a regulatory T cell depleting agent.