Abstract IA016: Enhancing adoptive T cell efficacy by elucidating and counteracting inhibitory factors in the tumor microenvironment

Abstract The development of optimized adoptive T cell-based therapies for ovarian cancer has advanced through integrated innovations in TIL (tumor-infiltrating lymphocyte) selection, genetic editing/engineering approaches, and chimeric antigen receptor (CAR) T cell design. In spite of these advances, as well as approvals of these cellular therapies for other malignancies, adoptive T cell therapy for ovarian cancer has not achieved the same level of efficacy. Enhancing T cell fitness and potency through the use of selection methodologies and/or genetic editing/engineering does provide one path towards improving outcomes, however, the ovarian cancer microenvironment is guarded by pro-tumor immune cells, suppressive ligand/receptor interactions and additional soluble factors that shutdown otherwise effective immune responses. Identifying and characterizing sources of immune suppression remains critical to the development of effective agents to counter these forces and is a major opportunity for the field. Our most recent data demonstrates that tumor-associated myeloid cells, long chain fatty acids and immune checkpoint receptors all play roles in dampening T cell responses, and that the creation of specific targeting agents and novel manufacturing strategies can overcome these suppressive barriers when combined with cellular immunotherapy, resulting in enhanced immune function and cancer regression. Collectively, the synergy of rationally-designed immune enhancing agents with refined TIL selection, advanced engineering, and/or CAR T targeting strategies offers a next-generation platform for potent and durable adoptive T cell therapies against ovarian cancer. Citation Format: Daniel J. Powell. Enhancing adoptive T cell efficacy by elucidating and counteracting inhibitory factors in the tumor microenvironment [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 IA016.