Therapeutic peptides
The present disclosure provides, in part, compositions comprising peptides that immunospecifically bind to a defined binding partner, such as MHC class I polypeptide-related sequence A (MICA), or an epitope thereon. In some embodiments, the peptides comprise one or more complementarity determining regions relating to the complementarity regions shown in Table 1. The disclosure also provides methods of treating cancer in a subject using the compositions disclosed herein, and methods of isolating human antibodies from cancer patients following immunotherapy.
1. A method of treating cancer in a subject, the method comprising administering a pharmaceutical composition comprising an antibody or antigen binding fragment thereof that binds to MHC class I polypeptide-related sequence A (MICA), wherein the antibody or antigen binding fragment thereof comprises a heavy chain variable region (V H ) and a light chain variable region (V L ) and wherein,
(a) the V H complementarity determining region 1 (CDR1) consists of the amino acid sequence of SEQ ID NO: 153,
the VH CDR2 consists of the amino acid sequence of SEQ ID NO: 156,
the VH CDR3 consists of the amino acid sequence set forth in SEQ ID NO: 158;
the VL CDR1 consists of the amino acid sequence of SEQ ID NO:160,
the VL CDR2 consists of the amino acid sequence of SEQ ID NO: 162, and
the VL CDR3 consists of the amino acid sequence of SEQ ID NO: 164; or
(b) the VH CDR 1 consists of the amino acid sequence of SEQ ID NO:208,
the VH CDR2 consists of the amino acid sequence of SEQ ID NO:210,
the VH CDR3 consists of the amino acid sequence set forth in SEQ ID NO: 212,
the VL CDR1 consists of the amino acid sequence of SEQ ID NO:215,
the VL CDR2 consists of the amino acid sequence of SEQ ID NO:217, and
the VL CDR3 consists of the amino acid sequence of SEQ ID NO:219.
2. The method of claim 1 , wherein the serum of the subject has elevated levels of the soluble MICA (sMICA) prior to administration of the pharmaceutical composition.
3. The method of claim 1 , wherein the cancer is melanoma, lung cancer, breast cancer, kidney cancer, ovarian cancer, prostate cancer, pancreatic cancer, gastric cancer, colon carcinoma, lymphoma or leukemia.