Figure 4.

Schematic representation of design of four generations of CAR. Legend: Conventional CARs: (A) 1st to 3rd generation are defined by their signaling domains: a primary signaling domain only (1st generation); signaling and co-stimulatory domains (2nd generation); combined co-stimulatory domains (3rd generation); a release of activating cytokine upon CAR engagement (4th generation). Co-expression of two different CARs: (B) engagement of either CAR triggers downstream activation (left); engagement of both CARs triggers downstream activation (right); (C) engagement of inhibitory CAR prevents T-cell activation in the presence of cells that express the target antigen 2.