Fig. 4.

Inhibitory CARs (iCARs) and their mechanism of action. Upon the interaction of iCAR T cells with healthy cells expressing the antigen recognized by the targeting domain of the iCAR construct, the inhibitory signaling cascades suppress the activation of the CAR T cells leading to minimization of on-target/off-tumor toxicities. On the other hand, upon the encounter of iCAR T cells with tumor cells and subsequent engagement with the activatory antigen (in the absence of the inhibitory antigen), genetically modified T cells achieve the necessary activation signals and eliminate the tumor cells. Made in ©BioRender—biorender.com