Hi-TIDe : T cell engineering

Our main research interest is the development of tumor-directed TCR- and CAR T cells that are programmed to logically respond to microenvironmental cues or/and small molecule administration for maximized function, fitness and safety. We have optimized retroviral, lentiviral and CRISPR-Cas9 based tools and methodologies, as well as T cell expansion conditions, allowing efficient evaluation of next-generation T cells in the context of both syngeneic and xenograft tumor models.

• We have optimized the transduction and expansion of murine CAR T cells for cancer immunotherapy (DOI: 10.1084/jem. 20192203). We are now using these tools to evaluate logic-based, next generation CAR designs for the treatment of syngeneic solid tumors in the context of a fully competent immune system. 

• In collaboration with Pr Olivier Michielin and Dr Michel Cuendet, and Pr Vincent Zoete we are comparing the efficacy of computationally designed TCRs (DOI: 10.1074/jbc. M112.357673) and of small molecule responsive T cell-signaling mediators for improved tumor control and safety.

• In collaboration with Pr Bruno Correia (EPFL, the Swiss Federal Institute of Technology in Lausanne), we have developed a novel STOP-CAR that can be remotely controlled by administration of a small molecule (DOI: 10.1038/s41587-019-0403-9). We are currently evaluating additional STOP-switch designs, as well as a novel ON-switch responsive to clinically approved molecules, for enhanced safety, as well as improved function via abrogation of CAR-T cell exhaustion.

• We have recently demonstrated that the function of VEGR-2 targeted CAR T cells is impaired by competition with soluble VEGF-A (JITC). We aim to elucidate factors in the solid tumor microenvironment that can inhibit CAR T cells and develop decoys/traps or signaling switch receptors to rescue/enhance their activity.