The first generation of CAR-T cells had the simplest architecture, i.e., an extracellular single-chain variable fragment (scFv) specific for a cancer marker; hinge and transmembrane regions usually derived from the CH2–CH3 region of IgG1, IgG4, or CD8; and the cytoplasmic CD3ζ signaling domain (Figure 3A) (76, 77). The gene discussed is CD8A; the disease is cancer.