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. Author manuscript; available in PMC: 2021 Dec 1.
Published in final edited form as: Curr Opin Biotechnol. 2020 Jul 24;66:88–94. doi: 10.1016/j.copbio.2020.06.008

Figure 1. Controllable CAR T cell designs.

Figure 1.

(a) Design of third generation CAR. A CAR is composed of an extracellular single-chain variable fragment (scFv) that specifically binds to the tumor associated antigen (TAA), co-stimulatory domain CD28 and 4–1BB, and the signal transduction immunoreceptor tyrosine-based activation motif (ITAM). (b) Design of SynNotch CAR. Upon cognate antigen A binding, SynNotch undergoes self-cleavage and release the transcription activator (TA) from the membrane. The TA then translocates into the nucleus and starts the CAR expression, which targets antigen B. (c) Design of Split CAR. The co-stimulatory domain 4–1BB and the signaling ITAM are separated into two molecules initially. When the small molecule Rapalog is added, FKBP and FRB dimerize, and the intact and functional CAR is formed. (d) Design of light inducible CAR. Upon light, LexA-CIB1-biLINus (LCB) translocate into the nucleus and bind to the promoter of CAR. At the same time, light can also induce the binding between LCB and CRY2-VPR (CV) to recruit a TA at the promoter region, which initiates CAR expression. Prom, promoter.