Immunotherapy with CAR-Modified T Cells: Toxicities and Overcoming Strategies

Figure 2

Summary of overcoming toxicities by the suicide gene co-expression in T cells. (a) HSV-tk turns the nontoxic prodrug GCV into GCV-triphosphate, leading to cell death by halting DNA replication. (b) iCasp9 can bind to the small molecule AP1903 and result in dimerization, which activates the intrinsic apoptotic pathway. (c) Targetable surface antigen expressed in the transduced T cells (e.g., CD20 and truncated EGFR), allowing eliminating the modified cells efficiently through complement/antibody-dependent cellular cytotoxicity (CDC/ADCC) after administration of the associated monoclonal antibody.