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WT CART5 (Wild Type CART5) is a chimeric antigen receptor (CAR) T-cell therapy targeting the CD5 antigen, developed by researchers at the University of Pennsylvania. The construct consists of a high-affinity single-chain variable fragment (scFv) targeting CD5, a CD8 alpha hinge and transmembrane domain, and a 4-1BB costimulatory domain linked to the CD3-zeta signaling chain. CD5 is a cysteine-rich scavenger receptor highly expressed in approximately 90% of T-cell lymphomas (TCL), 15-20% of acute myeloid leukemias (AML), and most cases of chronic lymphocytic leukemia (CLL) and mantle cell lymphoma (MCL). In research settings, "WT CART5" refers to the standard CAR-T product used as a baseline to compare against "CD5 KO CART5," which has the endogenous CD5 gene deleted via CRISPR-Cas9 to reduce fratricide and exhaustion. While WT CART5 demonstrates potent anti-tumor activity in preclinical models, it is associated with higher expression of exhaustion markers like PD-1 and LAG3 and reduced expansion compared to the gene-edited version.
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