Advanced chimeric antigen receptor designs such as SUPRA, UNI, Pro and Split have been applied to enhance control over engineered cells
| Structure | Description | Published example |
| SUPRA | Split, universal and programmable CAR system (SUPRA), the scFv and main CAR receptor are separate and become joined with a leucine zip. | Cho et al76 |
| UNI | Universal receptor as the common base, which is inactive. The binding domain of the injectable, interchangeable scFv binds to the uniCAR allowing full CAR T function. | Cartellieri et al,77 Ma et al78, Tamada et al,79 Urbanska et al80 |
| Probody/ masked CAR | Therapeutic receptor in which the active binding domain of the antibody is in an inactive form, which can become activated by tumor-associated proteases. | Han et al81 |
| Split | Antigen recognition motif is dissociated from the signaling motif of the CAR or signaling and costimulation domains are separated. | Rodgers et al,82 Kudo et al,83 Lanitis et al,84 Kloss et al85 |
CAR, chimeric antigen receptor; CRS, Cytokine Release Syndrome; scFv, short-chain variable fragment.