Abstract B100: An intrinsic safeguard for chimeric antigen receptor adoptive T-cell immunotherapies

Abstract

Abstract Adoptive CAR T cell therapies have been reported to be highly efficient at killing tumor cells and are on the verge of revolutionizing the field of cancer treatment. However, there are safety concerns with CAR T cell treatments which would require intervention, including on-target off-tumor effects, on-tumor toxicities such as cytokine release syndrome and tumor lysis syndrome. Avoiding the aformentionned acute and long term adverse events appears to be mandatory to improve the safety of adoptive cell immunotherapies. To address this issue, different teams developed molecular suicide switch systems to remove the transferred cell population. While these different systems are efficient at promoting eradication of adoptively transferred cells, they are expressed independent of the CAR. This could potentially lead to the generation of a CAR T population devoid of the suicide switch system raising concerns about their utility in the clinic. To address this issue, we developed a novel CAR architecture containing an integrated suicide switch component. We demonstrated that this CAR architecture was efficiently depleted by an FDA-approved molecule, retained its cytolytic potential and allowed for universal enrichment and detection of CAR T cells by GMP compatible kit. We will present its development and in-depth characterization. Note: This abstract was not presented at the conference. Citation Format: Julien Valton. An intrinsic safeguard for chimeric antigen receptor adoptive T-cell immunotherapies [abstract]. In: Proceedings of the Second CRI-CIMT-EATI-AACR International Cancer Immunotherapy Conference: Translating Science into Survival; 2016 Sept 25-28; New York, NY. Philadelphia (PA): AACR; Cancer Immunol Res 2016;4(11 Suppl):Abstract nr B100.