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. 2014 Nov 27;5:254. doi: 10.3389/fphar.2014.00254

Figure 1.

Figure 1

Mechanism of action of the different suicide gene technologies. (A) Suicide gene modification of cells of interest to allow conditional elimination in case of serious adverse events. Surface marker suicide genes, e.g., CD20, can also function as a selectable marker. (B) Dimerization induced e.g., iCasp9 protein with FKBP12-F36V binding domain joined to human caspase-9. Administration of AP1903 leads to dimerization of iCasp9 activating the intrinsic mitochondrial apoptotic pathway. (C) Metabolic, e.g., HSV/TK leads to phosphorylation of ganciclovir, and its triphosphate form (phosphorylated also through cellular kinases) incorporates into DNA with chain termination. (D) Monoclonal antibody (mAb) mediated, e.g., CD20 overexpression allows elimination after exposure to CD20 mAb through complement/antibody dependent cellular cytotoxicity (CDC/ADCC). LTR: long terminal repeat, psi: retroviral packaging element, iCasp9: inducible Caspase9, CARD: Caspase recruitment domain, HSVTK: herpes simplex virus thymidine kinase, GCV: ganciclovir, mAb: monoclonal antibody.