Compositions and methods for detecting, diagnosing, and treating cancer
The present invention provides compositions and methods useful for diagnosing, treating, and preventing cancer, particularly ovarian cancer and uterine cancer, based on the discovery that the oocyte specific protein, SAS1R (Sperm Acrosomal SLLP1 Receptor), which is a sperm protein receptor, is also expressed in various cancers, including ovarian cancer and uterine cancer. Six SAS1R variants have been previously identified, and they are encompassed by the invention. The present invention further provides antibodies useful for targeting SAS1R expressing cells and for killing such cells.
1. A method for treating SAS1R positive cancer comprising administering to a subject in need thereof an effective amount of an antagonist of SAS1R, thereby treating a SAS1R positive cancer,
wherein said cancer is selected from the group consisting of uterine cancer, lung cancer, head and neck cancer, pancreatic cancer, esophageal cancer, colorectal cancer, breast cancer, adenocarcinoma of the lung, squamous carcinoma of the lung, malignant mixed mullerian tumor, leukemia, and lymphoma,
wherein said antagonist of SAS1R activity is an antibody that binds to one or more SAS1R protein fragments selected from the group consisting of amino acids 1-25, 26-50, 51-75, 76-100, 101-125, 126-150, and 151-175 of SAS1R human variant 1 (SEQ ID NO:23).
2. The method of claim 1 , wherein said antagonist inhibits SAS1R activity, levels, or expression.
3. The method of claim 1 , wherein said antibody is selected from the group consisting of a single chain antibody, a monoclonal antibody, a bi-specific antibody, a chimeric antibody, a synthetic antibody, a polyclonal antibody, a humanized antibody, a fully human antibody, or active fragments or homologs thereof.
4. A method for inhibiting proliferation or killing a SAS1R positive cancer cell comprising contacting said cancer cell with an effective amount of antibody directed against SAS1R or a fragment thereof, wherein said antibody directed against SAS1R or a fragment thereof binds with SAS1R, thereby inhibiting proliferation or killing a cancer cell
wherein said cancer is selected from the group consisting of uterine cancer, lung cancer, head and neck cancer, pancreatic cancer, esophageal cancer, colorectal cancer, breast cancer, adenocarcinoma of the lung, squamous carcinoma of the lung, malignant mixed mullerian tumor, leukemia, and lymphoma,
wherein said antibody binds to one or more SAS1R protein fragments selected from the group consisting of amino acids 1-25, 26-50, 51-75, 76-100, 101-125, 126-150, and 151-175 of SAS1R human variant 1 (SEQ ID NO:23).
5. The method of claim 4 , wherein said killing is antibody-mediated complement-dependent cell killing.
6. The method of claim 4 , wherein said antibody is conjugated to another molecule or structure.
7. The method of claim 6 , wherein said molecule or structure is selected from the group consisting of an antibody, a protein, a pro-drug, a drug, a toxin, a protein toxin, a liposome, a radioactive isotope, and an enzyme.