Abstract A31: Comparing IL-12 and IL-18 secreting CAR T-cell efficacy

Abstract

Abstract MUC16, a subunit of CA125 that is overexpressed on epithelial ovarian cancers, can be targeted by T cells via the incorporation of the 4h11m28m chimeric antigen receptor (CAR) into the T-cell surface. However, the microenvironment of ovarian cancers consists of regulatory T cells, myeloid-derived suppressor cells, and tumor-associated macrophages that act to immunosuppress CAR T-cell function, thus abrogating CAR T-cell efficacy. To overcome this immunosuppression, our lab has developed IL-12 and IL-18 secreting CAR T cells, which have shown enhanced efficacy in a syngeneic ovarian cancer model when compared to second-generation CAR T cells. While IL-18 secreting CAR T cells have proven to be superior to IL-12 secreting CAR T cells in various leukemia and lymphoma mouse models, this observation does not translate to the ovarian cancer model. Mechanistic studies into the effects of IL-18 and IL-12 in a syngeneic ovarian cancer model are currently under way in order to better understand what each cytokine is doing to the tumor microenvironment as well as to the CAR T cell. With better understanding of the effects of IL-18 and IL-12, we can contribute to the immunobiology of these cytokines as well as harness their efficacy to apply to other tumor models. Citation Format: Christina E. Bebernitz, Renier J. Brentjens. Comparing IL-12 and IL-18 secreting CAR T-cell efficacy [abstract]. In: Proceedings of the AACR Special Conference on Tumor Immunology and Immunotherapy; 2018 Nov 27-30; Miami Beach, FL. Philadelphia (PA): AACR; Cancer Immunol Res 2020;8(4 Suppl):Abstract nr A31.