Abstract IA005: Regional combating of immunosuppressive forces in the ovarian tumor microenvironment

Abstract The accumulation of intraepithelial T cells in ovarian cancer is prognostic for increased survival while the accumulation of immunosuppressive cells, such as tumor associated macrophages, are associated with poor outcomes. These clinical findings provide the rationale for the development of immunotherapeutic approaches that locally augment T cell responses while circumventing immunosuppressive forces. Clinical trials of systemic immunotherapy have shown encouraging clinical responses in a subset of treated patients; however tumor regression does not occur in most treated patients, some patients experience immune related adverse effects and patients with immunologically cold tumors are unlikely to respond. One central objective of researchers is to understand the basis of natural immune recognition and to use this knowledge to rationally bolster anti-tumor immunity. One modality to augment anti-cancer immunity is to administer adoptive T cell therapy (ACT), thereby increasing the net number of tumor-reactive T cells in a patient. While ACT is effective and approved for the treatment of various hematological cancers, there is no approved immunotherapeutic agent for the treatment of ovarian cancer, including ACT. With significant advances in synthetic biology and large-scale cell manufacturing, it is now possible to generate patient-specific T cell products that specifically recognize and kill antigen expressing cancer cells; to outfit those T cells with supraphysiological properties that overcome immunosuppressive forces in the tumor microenvironment; and to safely promote local recruitment of endogenous T cell responses to markedly enhance the overall immune response against ovarian cancer. Using these techniques, overexpressed antigens can be targeted, immunosuppressive tumor associated macrophages can be selectively eliminated, the tumor microenvironment can be polarized to an inflammatory state, endogenous T cell recruited, and T cells made to proliferate robustly at the tumor site in response to tumor recognition. This knowledge and these approaches provide a guidepost and the infrastructure to begin creating safe and effective immunotherapy for ovarian cancer. Citation Format: Daniel J. Powell. Regional combating of immunosuppressive forces in the ovarian tumor microenvironment abstract. In: Proceedings of the AACR Special Conference on Ovarian Cancer; 2023 Oct 5-7; Boston, Massachusetts. Philadelphia (PA): AACR; Cancer Res 2024;84 (5 Suppl₂): Abstract nr IA005.