[Next generation engineered T cells for cell therapy: from lymphoma to solid tumors]

FDA approval and French ATU for chimeric antigen receptor (CAR) T cells represent an advanced step in the challenge of immunotherapy to cure cancer. The field of adoptive cell therapy emerged with the discovery that tumor-infiltrating-lymphocytes (TIL) can be used to treat melanoma patients. CAR T cells are engineered by gene transfer to express both receptors that target tumor-associated molecules and killing T cell functions. We report here how several decades of technology combining the specific recognition of an antibody with T cell function have led to the potent activity of CD19-targeting CAR KYMRIAH™ and YESCARTA™ i.e, high remission rates in patients with chemorefractory lymphoma. However, potentially fatal toxicity including cytokine release syndrome and neurotoxicity need next generation developments. Affinity fine-tuning, combinational CARs and guidelines for toxicity management are enhancing the safety of more powerful CAR T. Such CARs are emerging for solid tumor targeting. Synthetic biology approaches leading to personalized cell therapy marks the beginning of a new area.