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4SCAR19 is a fourth-generation chimeric antigen receptor (CAR) T-cell therapy developed by the Shenzhen Geno-Immune Medical Institute for the treatment of relapsed or refractory B-cell malignancies, including various forms of B-cell lymphoma and leukemia. The therapy involves the genetic modification of autologous T cells using a lentiviral vector to express a CAR construct specific to the CD19 antigen, which is widely expressed on B-cell lineage cells. The fourth-generation design is characterized by the inclusion of multiple intracellular signaling domains—specifically the CD28 transmembrane and cytoplasmic domain, the CD27 cytoplasmic domain, and the CD3ζ chain—to enhance T-cell activation, proliferation, and long-term persistence. Furthermore, 4SCAR19 incorporates an inducible caspase 9 (iCasp9) suicide safety switch, which can be activated to eliminate the CAR-T cells in the event of severe adverse effects such as cytokine release syndrome. It is often utilized as a foundational component of the '4SCAR2.0' multi-target regimen, where it may be administered alongside other CAR-T products targeting antigens like CD20 or CD22.
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