Abstract A065: Chimeric antigen receptor (CAR-T) cell therapy in ovarian cancer: Challenges and strategies for overcoming therapeutic barriers

Abstract The concept of CAR-T therapy was first put forward in the late 1980s. Chimeric Antigen Receptor (CAR) is a modified T cell-based immunotherapeutic system that redirects the T cell specificity against a selective number of antibody fragments. It functions in three different steps: recognition, fusion, and cell lysis. Generally, the T cell expresses the receptor on the surface of the cells that recognize and bind to the antigens produced by invading pathogens and rogue cancer cells in the human body. This CAR has unprecedented efficacy in solid tumors, most notably in ovarian cancer, with a preclinical regression rate of 70% with the application of the anti-PD-L1 and Mucin16 CAR-T cells. However, CAR-T immunotherapy has struggled over time against solid tumors. In this study, we have also focused on the challenges posed to CAR-T cell therapy by ovarian cancer, which can be overcome by the suitable application of the differentiation and exhaustion processes. Generally, a prospective combination of CAR with checkpoint blockade depletes the suppressive factors in the microenvironment. During this study, we have gone through 53 different articles that have been analyzed for the last 20 years (2004-2023). Our goal of the study is to address the major challenges of the CAR-T-based system in ovarian cancer and to analyze the successful applications of the CAR-T-based approaches. Citation Format: S. Danish Kadirr, Noushad Javed. Chimeric antigen receptor (CAR-T) cell therapy in ovarian cancer: Challenges and strategies for overcoming therapeutic barriers [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Advances in Ovarian Cancer Research; 2025 Sep 19-21; Denver, CO. Philadelphia (PA): AACR; Cancer Res 2025;85(18_Suppl):Abstract nr A065.