Fig. 2. Simultaneous targeting of two antigens may serve to enhances (Tandem CAR) or cut down (iCAR) the activity of the CAR-T cells.

Tandem CARs (TanCAR) mediate bispecific activation of T cells through the engagement of two chimeric receptors designed to deliver stimulatory or costimulatory signals in response to an independent engagement of two different tumor associated antigens (TAAs). iCARs use the dual antigen targeting to shout down the activation of an active CAR through the engagement of a second suppressive receptor equipped with inhibitory signaling domains