FIGURE 1.

Schematic representation of various approaches to improve safety of Chimeric antigen receptor T-cell constructs. Panel a: Biodegradable CAR-T cell. mRNA encoding disease-specific receptor genes is inserted into the T-cell by means of nanoparticles, electroporation, or photoporation. Panel b: suicide switch CAR-T cell. Activity is abrogated by the introduction of a small molecule or antibody that triggers the degradation of the T cell. Panel c: logic gated CAR-T. The construct has two binding domains for two separate targets, CAR-T activation is only initiated upon simultaneous binding of the CAR with both domains. Panel d: inducible CAR-T. Administration of specific molecules trigger the expression or functional assembly of the CAR. Panel e: MODULAR, switchable CAR-T on the left side the UniCAR having the epitope on the target module and on the right side Rev(ersible) CAR with the epitope expressed on the CAR-T cell. In both cases, the CAR can only be activated upon connection via the targeting component connecting the tumor cell with the Universal CAR. CAR-T, Chimeric antigen receptor T-cell.