Invited Talk

Predicting safety and efficacy of engineered T cells using an ex vivo human model

Institut Cochin, INSERM, U1016, CNRS, UMR8104, Université de Paris, France

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Adoptive transfer of T cells expressing chimeric antigen receptors (CARs) has shown remarkable clinical efficacy against advanced B cell malignancies. This clinical success has generated urgent interest in the development of new CARs and the extension of CAR T cell therapy to solid tumors that are, up to now, refractory to this strategy. Prior to initiating clinical trials, model systems in which CAR T cells can be characterized and tested for their potency and safety should be in place. To date, few models perfectly recapitulate the human immune system and tumor microenvironment, and some models have revealed CAR T limitations that were contradicted or missed entirely in other models. Thus, careful model selection is a crucial step in evaluating CAR T cell treatment and a major issue in the field of cancer immunotherapy. We have established a unique pre-clinical imaging platform based on slices from fresh human tumors that allows investigating, in a preserved tumor microenvironment, the efficacy of CAR-T cells. The possibility to use such a model to assess toxicity (e.g., on-target off-tumor) of engineered T cells will also be discussed.

Biosketch

Dr. Emmanuel Donnadieu Ph.D, is a group leader at INSERM Institut Cochin in Paris. His work uses fluorescence imaging techniques and ex vivo human 3D models to monitor T cell activities in human tumors. His current projects aim at targeting the tumor microenvironment to improve CAR T cell therapy.