[The new generations of CAR-T cells]

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.