Compositions and methods for inhibition of MICA/B shedding
The present invention is based, in part, on the discovery of monoclonal antibodies, and antigen-binding fragments thereof, that specifically bind to MICA/B α3 domain, as well as immunoglobulins, polypeptides, nucleic acids thereof, and methods of using such antibodies for diagnostic, prognostic, and therapeutic purposes.
1 . A method of blocking MICA/B antigen shedding on a cell, comprising contacting the cell with a monoclonal antibody, or antigen-binding fragment thereof, wherein the monoclonal antibody comprises:
(a) a heavy chain with three CDRs comprising amino acid sequences according to SEQ ID NO: 1, SEQ ID NO: 2, and SEQ ID NO: 3; and
(b) a light chain with three CD Rs comprising amino acid sequences according to SEQ ID NO: 4, SEQ ID NO: 5, and SEQ ID NO: 6;
wherein the monoclonal antibody, or antigen-binding domain thereof, binds a3 domain of MICA/B.
2 . The method of claim 1 , wherein the cell is a cancer cell, optionally wherein the cancer is selected from the group consisting of bladder cancer, breast cancer, uterine/cervical cancer, ovarian cancer, prostate cancer, testicular cancer, esophageal cancer, gastrointestinal cancer, pancreatic cancer, colorectal cancer, colon cancer, kidney cancer, head and neck cancer, lung cancer, stomach cancer, germ cell cancer, bone cancer, liver cancer, thyroid cancer, skin cancer, neoplasm of the central nervous system, lymphoma, leukemia, myeloma, sarcoma, and virus-related cancer.
3 . The method of claim 1 , wherein the cell is a human cell.