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PSMA ligand-fluorescein (also known as FITC-DUPA or DUPA-FITC) is a small-molecule conjugate consisting of a prostate-specific membrane antigen (PSMA) targeting ligand, 2-[3-(1,3-dicarboxypropyl)ureido]pentanedioic acid (DUPA), covalently linked to fluorescein isothiocyanate (FITC). Developed by Purdue University and Endocyte, it serves a dual role in oncology. As a diagnostic tool, it is utilized for the optical imaging of PSMA-positive prostate cancer cells and the detection of circulating tumor cells (CTCs) in peripheral blood. As a therapeutic adapter, it acts as a bispecific 'switch' or 'bridge' molecule in modular chimeric antigen receptor (CAR) T-cell or CAR-NK cell therapies. In this system, the DUPA moiety binds to PSMA on prostate cancer cells, while the fluorescein moiety is recognized by anti-fluorescein (anti-FITC) CAR-T or CAR-NK cells, bridging the immune cells to the tumor cells and triggering targeted cytotoxicity. This modular approach allows for precise control over CAR-T cell activation and helps mitigate toxicities such as cytokine release syndrome.
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