Category | CAR Control Technologies | Challenges Addressed | Mechanisms |
---|---|---|---|
1. Elimination of therapeutic cells | HSV-TK iC9 FADD CD20/Rituximab EGFRt/Cetuximab Cytosine deaminase Death signalobody, SFas Uridine metabolic switch | Safety | Incorporated genetic mechanism for on-demand cell elimination |
2. Regulation of CAR gene expression | Tet-ON Res controlled CAR Zinc finger TF-based switch system LINTAD ReCoM Photothermal switch CAR FUS-CAR system HiCAR HypoxiCAR SynNotch logic CAR | Safety Efficacy Flexibility | Spatiotemporal control of CAR abundance limits off-tumor activity Prevent T cell exhaustion Controlling CAR expression location or using AND-logic provides access to more target antigens |
3. Inducible CAR protein degradation | SWIFF-CAR Lenalidomide-induced CAR degradation PROTAC-mediated CAR degradation | Safety | Temporal regulation of CAR protein activity and abundance |
4. Inducible formation of a functional CAR or inducible CAR disassembly | ON-switch split CAR DARRIC AvidCAR Lenalidomide ON switch split CAR Lipocalin-based ON-switch CAR FKBP/FRB-mcCAR LiCAR CRASH-IT switch CAR STOP-CAR Minocycline TetCAR CondCAR OFF-switch CAR | Safety Efficacy | Temporal regulation of CAR protein activity and abundance Prevent T cell exhaustion |
5. Inhibitory CARs | iCAR Double-Arm CAR iKP (KIR2-PD1) CAR Tmod2 CAR NASCAR anti-HLA-DR iCAR | Safety Efficacy Flexibility | Limited off-tumor CAR activity Improved precision of antigen targeting More target antigens available (NOT-logic) |
6. Modular universal adaptor CAR platforms | FcR-based ADCC CAR Anti-FITC CAR BBIR CAR mSA2 CAR AdCAR PNE specific CARs Convertible CAR Cp-Fab CAR SpyCatcher CAR SNAP-CAR UniCAR RevCAR SUPRA CAR bsCAR | Safety Efficacy Flexibility | Dose-dependent control of CAR abundance Simultaneous targeting of multiple antigens available Modular design for easy antigen retargeting |