Abstract 1149: Universal redirection of chimeric antigen receptor T cells against solid tumors via tumor cell membrane-inserting CAR ligands

Abstract

Abstract Chimeric antigen receptor (CAR) T cell therapy is effective in treating certain hematological malignancies, but its translation to solid tumors has been challenging. Selecting an effective target antigen is hampered by heterogeneous tumor antigen expression and target antigen expression in healthy tissues. We describe a strategy to promote CAR T-mediated destruction of any tumor via intratumoral administration of a membrane-inserting fluorescein isothiocyanate lipid amphiphile molecule (“amph-FITC”) recognizable by a FITC-specific CAR. Firstly, we show labeling of tumor cells with amph-FITC in vitro, mediating cytotoxicity by FITC CAR T cells in coculture. Then, we demonstrate efficient tagging of tumor cells in vivo upon intratumoral injection with minimal labeling of non-tumor tissues, driving FITC CAR T cell proliferation and accumulation in tumors. Subsequently, we determine that this strategy stimulates an anti-tumor response that facilitates tumor regression in several syngeneic and human xenograft mouse models bearing different tissues of origin. In syngeneic models, this strategy induced the infiltration of host T cells and elicited endogenous tumor-specific T cell priming, leading to protection against tumor rechallenge. These results demonstrate the capacity to treat tumors independent of antigen expression or tissue of origin, addressing a major bottleneck in adoptive T cell therapy. Citation Format: Angela Zhang. Universal redirection of chimeric antigen receptor T cells against solid tumors via tumor cell membrane-inserting CAR ligands [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 1149.