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.
- Evripidis Lanitis, Paris Kosti, Catherine Ronet, Elisabetta Cribioli, Giorgia Rota, Aodrenn Spill, Patrick Reichenbach,Vincent Zoete, Denarda Dangaj Laniti, George Coukos, Melita Irving. VEGFR-2 redirected CAR-T cells are functionally impaired by soluble VEGF-A competition for receptor binding. Journal for Immunotherapy of Cancer (2021)
- Evripidis Lanitis, Giorgia Rota, Paris Kosti, Catherine Ronet, Aodrenn Spill, Bili Seijo, Pedro Romero, Denarda Dangaj, George Coukos, and Melita Irving. Optimized gene engineering of murine CAR-T cells reveals the beneficial effects of IL-15 coexpression JEM (2021)
- Giordano-Attianese, G., Gainza, P., Gray-Gaillard, E., Cribioli, E., Shui, S., Kim, S., Kwak, M. J., Vollers, S., Corria Osorio, A. J., Reichenbach, P., Bonet, J., Oh, B. H., Irving, M., Coukos, G., and Correia, B. E. A computationally designed chimeric antigen receptor provides a small-molecule safety switch for T-cell therapy. Nat Biotechnol (2020)
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