Fig. 1.

Generation of the chimeric antigen receptor (CAR) and various designs. The prototype of CAR used the variable region (V) of the heavy (H) and light (L) chains from an antibody. The whole complex was assembled as a TCR complex with other CD3 subunits. The 1st generation CAR was streamlined to became the single-chain version. To date, the 2nd generation and 3rd generation CARs have been most commonly used. These proteins contain additional costimulatory signaling domains from CD28 and 4-1BB. All of the designs are based on CD3ζ being the T cell-signaling initiator, which requires phosphorylation by a Src family kinase