Previously, Roybal and colleagues (43) constructed engineered T cells with synNotch receptors, in which Notch-ECD was replaced with a single-chain variable fragment (scFv) against cancer antigens such as CD19 and HER2, and Notch-ICD was replaced with the Gal4 DNA binding domain fused to the tetrameric viral transcriptional activator domain, VP64 (47). The gene discussed is CD19; the disease is cancer.