Abstract 2330: Preclinical evaluation of TC-110: CD19-specific T cell receptor (TCR) fusion construct (TRuC™) T cell for the treatment of hematologic malignancies

T cells expressing chimeric antigen receptors (CARs) have demonstrated clinical benefit in certain hematological malignancies albeit with disease relapse as well as side effect such as cytokine release syndrome. To overcome potential hurdles of CAR-T cells and other T cell receptor modalities, we have designed a novel T cell engineering platform. Specifically, we have generated T Cell Receptor Fusion Constructs (TRuC™) that fuse a binder domain to subunits of the T cell receptor. These constructs when introduced using lentiviral technology, integrate into endogenous TCR, reprograming T cells to target tumor antigen in a non-major histocompatibility complex (MHC) restricted fashion and harnessing the full spectrum of TCR signaling. Here, we present the results of the preclinical evaluation of TC-110, a CD19-specific e-TRuC™ variant. In vitro, TC-110 T cells are equally potent as CAR T cells in eliminating tumor cells, while producing less inflammatory cytokines. In preclinical mouse models of ALL and Burkitt’s lymphoma, TC-110 T cells demonstrate better efficacy than 2nd generation CAR-T cells bearing CD28 or 41BB co-stimulatory domains. Of note, the efficacy of TC-110 T cells, both in vitro and in vivo, is not dependent on co-stimulatory signal. Overall, we demonstrate the efficacy of TC-110 T cells both in vitro and in preclinical mouse models, indicating the clinical potential of TRuC™ platform for treating hematologic malignancy. Citation Format: Holly Horton, Jian Ding, Seema Shah, Jessica Gierut, Niko Thorausch, Anna Morath, Wolfgang Shamel, Marcela Maus, Patrick Baeuerle, Robert Hofmeister, Daniel R. Getts. Preclinical evaluation of TC-110: CD19-specific T cell receptor (TCR) fusion construct (TRuC™) T cell for the treatment of hematologic malignancies [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 2330.