Fig. 6.

Safety switch strategies for increasing the safety index of CAR T cells and their mechanism of action. a iCasp9 safety suicide and its mechanism of action. The activation of inducible caspase 9 is mediated upon the introduction of a small synthetic dimerizing agent leading to the activation of downstream apoptotic pathways and selective elimination of the CAR T cells equipped with this switch. b Herpes simplex virus thymidine kinase (HSV-TK) safety switch and its mechanism of action. Upon the introduction of ganciclovir, HSV-TK catalyzes it to ganciclovir-monophosphate (MP) which will eventually be modified to ganciclovir-trisphosphate (TP). Furthermore, TP will mediate the inhibition of DNA synthesis leading to the selective elimination of the T cells harboring this safety switch. Made in ©BioRender—biorender.com