HERV-K antibody therapy

Abstract

This invention provides antibodies, cells, and methods for treating cancer for use in immunotherapy. [Solution] The present invention provides therapeutic humanized anti-HERV-K antibodies, bispecific T cell engagers (BiTEs) against CAR or CD3 and CDS, DNA-encoding BiTEs (DBiTEs), or antibody-drug conjugates (ADCs) comprising the same. The present invention also relates to peptides, proteins, nucleic acids, and cells for use in immunotherapy. In particular, the present invention relates to immunotherapy of oncocyte peptides or peptides that may also be targets of antibodies and other binding molecules bound to MHC molecules.

Claims

1. An isolated antibody that binds to human endogenous retrovirus-K (HERV-K), comprising a heavy chain variable region (HCVR) and a light chain variable region (LCVR).

2. The antibody according to claim 1, comprising a humanized or human framework region.

3. The antibody according to claim 1, which is a HERV-K antagonist.

4. The antibody according to claim 2, for use in reducing tumor growth.

5. The antibody according to claim 2, for use in reducing metastasis to the lungs, lymph nodes, or other organs.

6. An isolated nucleic acid comprising a nucleotide sequence encoding HCVR, LCVR, or a combination thereof as described in claim 1.

7. An expression vector comprising the nucleic acid described in claim 6.

8. A host cell transformed with the expression vector described in claim 7.

9. A method for treating cancer in a mammal, comprising administering an effective amount of the antibody described in claim 2 to a mammal in need thereof.

10. The method according to claim 9, wherein the antibody is conjugated via a linker to a cytotoxic drug, auristatin or a functional peptide analog or derivative thereof.

11. The method according to claim 9, wherein the cancer is selected from the group consisting of melanoma, chronic lymphocytic leukemia, breast cancer, pancreatic cancer, head and neck cancer, ovarian cancer, cervical cancer, colorectal cancer, testicular cancer, stomach cancer, kidney cancer, endometrial cancer, uterine cancer, bladder cancer, prostate cancer, esophageal cancer, liver cancer, and non-small cell lung cancer.

12. The method according to claim 9, wherein the antibody is a full-length antibody.

13. The method according to claim 9, wherein the antibody is a human monoclonal IgG1 or IgG4 antibody.

14. Humanized antibodies for use in CAR T, CAR NK, or BiTE assays.

15. Humanized antibodies for use in CAR T, CAR NK, or BiTE assays, which are used to develop CAR T, CAR NK, or BiTE.

16. Cancer cells overexpressing HERV-K, for use as a target for the anti-HERV-K humanized antibody and ADC of the present invention.

17. hu6H5 clones (FWJ1 and FWJ2) generated from bacteria (HUM1 and HUM2) or mammalian cells.

18. A BiTE directed against humanized scFv against T cell CD3 or CD8 and tumor-associated antigen HERV-K, comprising an antibody targeting either CD3 or CD8 and HERV-K.

19. T cells expressing a lentiviral CAR expression vector containing humanized or fully human HERV-K scFv.

20. Humanized single-chain variable fragment (scFv) antibodies capable of binding to antigens generated from recombinant HERV-K Env surface fusion protein (KSU) and to lysates from cancer cells expressing HERV-K Env protein.

21. A CAR generated from a humanized scFv as described in claim 19.

22. An improved in vivo enrichment method for rapid expansion and proliferation and B cell activation in donors lacking memory B cells, (a) A step of treating mice with a cytokine cocktail on days 1, 7 and 14, and (b) Step of boosting the immunization of mice with the antigen on days 14 and 21. Methods that include...

23. Cells that produce antibodies that can bind to antigens and kill cancer cells.

24. A method for blocking the immunosuppressive domain (ISD) using a HERV-K immune checkpoint inhibitor.

25. The method according to claim 42, wherein the HERV-K immune checkpoint inhibitor is selected from the group consisting of monoclonal antibodies and drugs that target the ISD of HERV-K.

26. Humanized and fully human antibodies targeting HERV-K for use in enhancing the efficacy of checkpoint-blocking antibody treatment.

27. A method for generating antibodies from immunized mice using five multi-antigen peptides (MAPS) produced from HERV-KSU protein produced by cancer patients.

28. HERV-K CAR A: A method for generating VH-VLhu6H5-CD8-CD28-4-1BB-CD3 zeta.

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