Fig. 2

First, second and third generation CARs. First generation CARs consist of an antigen-binding scFv fused via a hinge to the transmembrane and activation domain from CD3ζ. Second generation CARs use a variety of hinges and transmembrane domains, plus a single costimulatory domain in addition to the antigen-binding scFv and CD3ζ activation domain. This enables them to recapitulate the two signals required for full T-cell activation. Third generation CARs build on the basic structure of the second generation CAR by adding a second costimulation domain. Created with BioRender.com