Figure 2: Basic design of chimeric antigen receptors. Chimeric antigen receptors (CARs) consist of an antigen binding domain, a spacer/hinge region, a transmembrane domain, and an endodomain that consists of domains derived from costimulatory molecules and CD3-z. Depending on the number of costimulatory endodomains, CARs are designated as 1st generation (no costimulatory domain), 2nd generation (one costimulatory domain), 3rd generation (two costimulatory domain).