Abstract A072: Altering the ovarian cancer tumor microenvironment using car t cell therapy

Abstract

Abstract Ovarian cancer accounts for 12,810 deaths per year in the USA, making it the deadliest gynecologic malignancy. Unfortunately, patients who are resistant to standard of care treatments have very limited effective therapeutic options. Immunotherapies are an emerging class of treatments that utilize a patient’s immune system to recognize and destroy tumor cells and have resulted in dramatic responses in many hematologic malignancies. In particular, reprograming patient T cells to recognize specific surface antigen(s) known as chimeric antigen receptor (CAR) T cell therapy, has provided both pediatric and adult patients with relapsed or treatment-unresponsive hematologic malignancies novel and potentially curative treatment options. CAR T cell therapy received FDA approval in 2018 for the treatment of B cell leukemia, however despite significant efforts, has been largely ineffective in solid malignancies. This is due in part to the complex solid tumor immune microenvironment (TME) and how it may change in response to therapies. For example, there is evidence that an FDA approved treatment for ovarian cancer called poly(ADP) ribose polymerase inhibitors (PARP; PARPi) leads to increased immune cell infiltration and cancer sensitivity to immunotherapies. This proposal will delineate the immune composition of the ovarian cancer TME using mouse models that closely recapitulate ovarian cancer progression and examine the impact of CAR T cells on the TME. We will utilize mouse ovarian cancer models that are sensitive and resistant to PARP inhibition. The information derived from these studies will provide a better understanding of the evolution of ovarian cancer TME and provide insight on how CAR T cells may alter the TME. Ultimately, we hope this work will lead to the development of safer and more effective therapeutic options for ovarian cancer patients. Citation Format: Alexandra N. McMellen, Michael S. Leibowitz. Altering the ovarian cancer tumor microenvironment using car t cell therapy [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 Suppl_2):Abstract nr A072.