Grant: Project Grant

Over 70% of ovarian cancer patients are diagnosed with advanced (stage III & IV) disease which has a five-year survival rate of 30%. The 5-year survival of patients with advanced pancreatic cancer is 8%. Recent clinical trials using novel precision medicine approaches such as immunotherapies have not yielded encouraging results for ovarian cancer patients. On the other hand, Keytruda an immune checkpoint inhibitor is approved in combination with chemotherapy for pancreatic cancer with modest benefits. MUC-16 is overexpressed in 80% of epithelial ovarian cancers (EOC) and 65% of pancreatic cancer. MUC-16 is responsible for the aggressiveness and drug resistance of EOC and pancreatic cancer. Therefore, this protein can serve as a target for the diagnosis and treatment of these cancers. Very few attempts at using MUC-16 as a therapeutic target against EOC and pancreatic cancer have been pursued in clinical trials. This work will focus on developing and testing new diagnostic and therapeutic agents against MUC-16 positive EOC and pancreatic cancer. We will develop a new fully human antibody conjugate that is tagged with potent radioisotopes actinium-225 (225Ac) effective enough to eliminate primary and metastatic tumor cells that express this protein. These new therapeutics will be tested in patient-derived organoids (3D cancer tissue grown on plates) and in different mouse models. We will investigate if these radiolabeled antibodies can prime tumor immune cells, and take advantage of this by combining the radiolabeled antibody with immune checkpoint inhibitor such as Keytruda® for enhanced efficacy. This compound will be labeled with zirconium-89 (89Zr) for PET/CT imaging. It is the hope that this will improve the survival of EOC and pancreatic cancer patients when translated in clinical trials.