Fig. 2
From: Synthetic biology approaches for improving the specificity and efficacy of cancer immunotherapy
Tunable switches for controlling CAR-T-cell activity. A The design of an “ON-switch”. This type of design splits a conventional CAR into two individual components. Upon the administration of a small molecule drug, both components will assemble into a functional CAR and enable T cells to be activated by the target antigen. B An “ON-switch” CAR based on lenalidomide-induced receptor dimerization. Lenalidomide induces dimerization of an IKZF3 variant and a CRBN variant, leading to functional CAR formation that can be activated by the target antigen. C The design of the LiCAR. This design utilizes light-inducible dimerization of LOV2-ssrA and sspB to control the assembly of two separate CAR chains into a functional chain that can be activated by the target antigen. D The design of an “OFF” switch. This design consists of two separate CAR components and can naturally form a functional CAR. When a small molecule drug is administered, the functional CAR will disassemble and lose its function. E The design of an “OFF” switch based on small molecule-induced protein degradation. An IKZF3-based degron is tagged at the CAR. When lenalidomide is administered, it recruits the CRL4CRBN E3 ubiquitin ligase to trigger the degradation of CAR
