Les nouvelles générations de cellules CAR-T

The new generations of CAR-T cells

¹ Dynamics of intracellular organization laboratory, Institut Curie, PSL Research University, Sorbonne Université, CNRS, UMR144, Paris, France
² Cell therapy Acceleration and Innovation (CellAction), Institut Curie, Suresnes, France

^* zelia.gouveia@curie.fr

Résumé

L’approche CAR-T, qui consiste à utiliser des lymphocytes T exprimant un récepteur de l’antigène recombinant (CAR, pour chimeric antigen receptor) permettant d’éliminer les cellules présentant un antigène particulier, est l’une des immunothérapies les plus prometteuses pour soigner les cancers. L’ingénierie des CAR-T a évolué au fil de leurs générations, pour renforcer leur activité et leur spécificité, et surmonter leurs limites, comme leur faible persistance, leur toxicité et leur inefficacité dans la lutte contre les tumeurs solides. Cette revue explore les différentes générations de CAR, les tests cliniques en cours sur le cancer et les maladies auto-immunes, ainsi que les limites associées aux cellules CAR-T dans le traitement des cancers.

Abstract

Chimeric antigen receptor (CAR)-T is one of the most promising modern cancer immunotherapies. In the recent years, impressive results have been obtained in the treatment of cancer which led to FDA approval for the treatment of liquid tumors. In this cell-based therapy, immune cells (e.g. T and NK cells) are engineered to express a synthetic receptor CAR to specifically recognize and eliminate cells expressing a target antigen.

CAR has evolved through different generations aiming to boost its biological activity and overcome limitations such as low persistence, limited potency, life-threatening toxicity and inefficient activity against solid tumor. The present review provides an overview of the different CAR generations, starting from the 1^st generation with limited cytotoxic activity until the latest generation, the 5^th generation or new generation, developed to overcome various limitations of CAR T therapy. The current ongoing clinical trials in cancer and autoimmune diseases, and the limitation associated with CAR-T cells in cancer therapy, are also discussed.