Fig. 1.

Evolution of CAR structure throughout different generations. First generation of CARs contains only antigen recognition domains and CD3ζ activation domain. Second generation of CARs additionally comprises a co-stimulatory domain (such as 4-1BB or CD28). In the third generation, two co-stimulatory domains are included. T cells expressing fourth generation CAR (sometimes called TRUCKs) contain an additional cDNA cassette, e.g., encoding an immunomodulator. Fifth generation of CARs is a group of next gen receptors, such as ON-switch CARs (on the figure above), the universal CAR-T cells, etc., all aiming at improving safety and efficiency of immunotherapies