CAR T Cells: A Snapshot on the Growing Options to Design a CAR

Adoptive cell therapy of malignant diseases with chimeric antigen receptor (CAR) modified T cells rapidly advanced from pre-clinical models to commercial approvals within 2 decades. CARs redirect patient's T cells towards cancer cells and activate the engineered cells for a cytolytic attack resulting in the destruction of the cognate target cell. CAR T cells have demonstrated their powerful capacities in inducing complete and lasting remissions of leukemia/lymphoma in an increasing number of trials worldwide. Since the early 90's, the design of CARs went through various steps of optimization until the very recent developments which include CARs with logic gating in the recognition of antigen patterns on target cells and TRUCKs with a target recognition induced delivery of immune modulating agents. Here we review the generations in CAR design, the impact of specific modifications, the strategies to improve the safety of CAR T cell therapy, and the challenges to adapt the CAR design for broader applications.