Figure 1.

Activation of T-cells and CAR T-cells. The left half of the diagram depicts signals necessary for T-cell activation. (1) Interaction between major histocompatibility complex (MHC) of antigen presenting cell (APC) and T-cell receptor (TCR) of T-cell. Anergy will result if only signal (1) is given. (2) Interaction between co-receptors such as CD28 between APC and T-cell. Co-presentation of signal (1) and (2) are necessary for T-cell response. (3) Interaction between cytokines released by APC and receptors on T-cell. Signal (1), (2) and (3) will result in robust activation of T-cell. Right side depicts evolution of CAR T-cell design. (1) Generation 1 CAR T-cells with intracellular CD3 domain; (2) Generation 2 with intracellular CD28 and CD3 intracellular domain; (3) Generation 3 with additionally intracellular signaling domains. Each generation has increased level of activation.