Fig. 3 Conditionally expressed CAR using Notch as a signal induction and response pathway system. Conditionally expressed CAR using Notch as a signal induction.

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Fig. 3 Conditionally expressed CAR using Notch as a signal induction and response pathway system. Conditionally expressed CAR using Notch as a signal induction and response pathway system. The extracellular ligand-binding domain of CAR 1, upon engagement with its cognate ligand (i), induces proteolysis of the intracellular domain of a synthetic Notch (synNotch) receptor, which contains a transcriptional regulator. Upon release, the notch intracellular domain is translocated to the nucleus (ii) to regulate transcription (iii) of the gene encoding CAR 2 downstream of the transcription factor binding site. Translation of the protein (iv) is followed by the surface expression of the CAR (v). In this manner, a conditional CAR expression specific to a second antigen in the presence of the first antigen–specific ligand safely arms the T cell for highly specific recognition. Carl H. June et al. Science 2018;359:1361-1365 Copyright © 2018 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works