Mary “Nora” Disis, MD, on Reevaluating the Potential of CAR-T Approaches in Ovarian Cancer

“CAR T-cell products in the ovarian cancer space have been tested and haven't seemed to be that effective. They were done with first-generation technologies and 1 of the major problems was that they really didn't persist in the body, and so they really didn't have much of an antitumor effect. I think with strategies such as this that are engineering agents to help those CART-cell products persist we'll start seeing clinical efficacy with these products in ovarian cancer.”

Several clinical trials have evaluated various chimeric antigen receptor T-cell (CAR-T) therapies to treat patients with ovarian cancer. Because these initial efforts did not meet much success, some researchers and institutions have been hesitant to continuetrying new CAR-T approaches in this space, despite the great unmet need that remains for patients with advanced stage platinum-resistant ovarian cancer.

In an interview with CGTLive™’s sister publication OncLive®, Mary “Nora” Disis, MD, director of University of Washington Medicine’s Cancer Vaccine institute, discussed need to continue exploring CAR-T approaches in ovarian cancer and explained the potential that these advanced therapies have in treating solid tumors when certain obstacles are addressed. Disis coauthored a study entitled “Phase 1/1b study of PRGN-3005 autologous UltraCAR-T cells manufactured overnight for infusion next day to advanced stage platinum resistant ovarian cancer patients," which was presented at the American Society of Clinical Oncology (ASCO) 2023 Annual Meeting, held June 2-6, in Chicago, Illinois. The presentation covered promising early results from a phase 1/1b clinical trial (NCT03907527) evaluating PRGN-3005, an investigational CAR-T product that targets MUC16 and has been designed with features intended to increase persistence of the CAR T-cells. Disis noted that persistence of CAR T-cells has been a major limitation in previous attempts to apply CAR-T approaches in ovarian cancer. She also spoke about the potential of immunotherapy combination treatments to improve outcomes in solid tumors and discussed the importance of evaluating CAR-T therapies in earlier treatment settings than those typically used in phase 1 trials.

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REFERENCE
1. Liao JB, Stanton SE, Chakiath M, et al. Phase 1/1b study of PRGN-3005 autologous UltraCAR-T cells manufactured overnight for infusion next day to advanced stage platinum resistant ovarian cancer patients. Presented at: the American Society of Clinical Oncology (ASCO) 2023 Annual Meeting, held June 2-6, in Chicago, Illinois. Abstract #5590