Figure 6.

Natural and engineered combinatorial T-cells. A, Natural T-cell with its T-cell receptor, targeting only single antigens. This single-antigen recognition without any further control machinery can lead to off-target tissue damage. B, An engineered synthetic T-cell with new types of receptors specific for detecting given combinations of antigens. Upon binding of antigen A to the synNotch receptor, an orthogonal transcription factor is cleaved from the cytoplasmic tail of the receptor, which in turn activates CAR transcription. If a second antigen, antigen B, is recognized by the newly synthesized CAR receptor, the T-cell is activated. (Adapted from Roybal et al., 2016; Roybal and Lim, 2017.)