Roybal and colleagues [36] previously engineered T cells equipped with synNotch receptors where the extracellular domain (ECD) of Notch was substituted with a single-chain variable fragment (scFv) targeting cancer antigens like CD19 and HER2, and the intracellular domain (ICD) was replaced with a fusion of the Gal4 DNA binding domain and the VP64 tetrameric viral transcription activator domain [40]. The gene discussed is CD19; the disease is cancer.