AAV9 Gene Therapy using a Novel Engineered MIS to Treat Ovarian Cancer

Ovarian cancer is the most lethal malignancy of the female reproductive tract with few treatment options. MIS has previously been shown to inhibit growth of a stem-like subset of the total cancer cell population in ovarian cancer lines. We have recently engineered novel peptide modifications to human MIS LR-MIS, which increase production and potency in vitro and in vivo, and inserted it into an AAV9 vector. AAV delivered gene therapy has undergone a clinical resurgence with a good safety profile and sustained gene expression. Therefore, we propose to evaluate the efficacy of a single dose of AAV9-LRMIS to inhibit chemoresistant recurrences in a patient-derived ovarian cancer xenografts PDX model of surgical debulking followed by chemotherapy. To evaluate the potential responsiveness of the patient population and elucidate the mechanism of action we will analyze gene expression changes in primary cell lines treated with LRMIS.