Figure 1.

The illustration of the disposition of adoptive cell therapy side effects. (A) An epitope is expressed on CAR-T or TCR-T cells, which can be recognized by epitope-targeted antibodies, thus leading to CAR-T or TCR-T cells being killed through antibody-mediated cytotoxicity. (B) The addition of a dimerizing drug activates iCasp9 signaling and leads to apoptosis. (C) The reduced affinity of TCR/CAR can enhance specificity and reduce off-tumor on-target cytotoxicity. (D) The construction of switchable CAR is an effective method to reduce the side effects of CAR-T therapy; the strategy is to separate the antigen-binding domain from the signal transduction domain through a peptide neoepitope (PNE) that works as a bridge between the antigen-binding domain and the signal transduction domain. (E) On binding one tumor antigen, the synNotch receptor undergoes a conformational change that leads to the release of a transcription factor, which in turn drives the expression of a CAR-T antigen for another inhibitory antigen. (F) Inhibitory CAR (iCAR) dampens the T cell response when a normal antigen is encountered. (G) OR gate CAR is comparable to bispecific CARs.