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N4CART is an experimental second-generation chimeric antigen receptor (CAR) T-cell therapy designed to target Nectin-4, a cell adhesion molecule frequently overexpressed in solid tumors such as breast, urothelial, and colon cancers. The therapy utilizes a single-chain variable fragment (scFv) that specifically recognizes a tumor-specific antigenic variant (TSAV) of Nectin-4, which is absent in the Nectin-4 expressed by healthy skin keratinocytes. This selective targeting is intended to mitigate the severe skin toxicities commonly associated with other Nectin-4-targeted agents, such as the antibody-drug conjugate enfortumab vedotin. N4CART cells are engineered using baboon-envelope pseudotyped lentiviral vectors, which have demonstrated superior transduction efficiency in αβ T cells compared to standard VSVG-pseudotyped vectors. Preclinical studies in cell-derived and patient-derived xenograft models have shown that N4CART can induce remissions and effectively kill tumor cells that are resistant to enfortumab vedotin.
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