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.
- Herrera, F. G., Ronet, C., Ochoa de Olza, M., Barras, D., Crespo, I., Andreatta, M., Corria-Osorio, J., Spill, A., Benedetti, F., Genolet, R., Orcurto, A., Imbimbo, M., Ghisoni, E., Navarro Rodrigo, B., Berthold, D. R., Sarivalasis, A., Zaman, K., Duran, R., Dromain, C., Prior, J., Schaefer, N., Bourhis, J., Dimopoulou, G., Tsourti, Z., Messemaker, M., Smith, T., Warren, S. E., Foukas, P., Rusakiewicz, S., Pittet, M. J., Zimmermann, S., Sempoux, C., Dafni, U., Harari, A., Kandalaft, L. E., Carmona, S. J., Dangaj Laniti, D., Irving, M., and Coukos, G. Low-Dose Radiotherapy Reverses Tumor Immune Desertification and Resistance to Immunotherapy. Cancer Discov (2022)
- 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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