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CD33-CAR-28z1XX is an experimental second-generation chimeric antigen receptor (CAR) T-cell therapy designed to target the CD33 antigen, a cell surface protein highly expressed on the blasts of most patients with acute myeloid leukemia (AML). The construct features a CD28 costimulatory domain and a modified CD3zeta signaling domain known as "1XX." Developed at Memorial Sloan Kettering Cancer Center, the 1XX technology involves mutating two of the three immunoreceptor tyrosine-based activation motifs (ITAMs) in the CD3zeta chain, leaving only the membrane-proximal ITAM functional. This modification is intended to calibrate T-cell activation, providing a balanced signal that enhances therapeutic potency and T-cell persistence while reducing the risk of premature T-cell exhaustion compared to standard CD3zeta-based CARs. The construct often includes a truncated human EGFR (EGFRt) as a tracking and potential safety switch component.
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