Abstract A064: Nanocarrier-mediated siRNA delivery to boost CAR-T cell therapy in tumor microenvironment-driven immune dysregulation in ovarian cancer

Abstract The tumor microenvironment (TME) significantly influences tumor proliferation and therapeutic resistance, particularly through complex interactions between its components and immune cells. In ovarian cancer, the TME supplies essential nutrients and physical space for tumor growth while suppressing immune responses. The infiltration of effector T cells within this heterogeneous environment often leads to impaired T cell activation, reduced proliferation, and exhaustion, eventually affecting the anti-tumor immunity. These challenges impose major obstacles to the success of CAR-T cell therapy in solid tumors. However, recent in vivo studies suggest that nano-drug delivery of curcumin via siRNA, with CAR-T therapy, can enhance therapeutic efficacy by up to 90%. This analysis aims to highlight the key physiological and immunological barriers limiting CAR-T effectiveness in solid tumors and proposes combinatorial approaches to improve therapeutic outcomes in ovarian cancer and related malignancies. Citation Format: S. Danish Kadirr, Noushad Javed. Nanocarrier-mediated siRNA delivery to boost CAR-T cell therapy in tumor microenvironment-driven immune dysregulation in ovarian cancer 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 (18Suppl): Abstract nr A064.