A fluorescent, [18F]-positron-emitting agent for imaging PMSA allows genetic reporting in adoptively-transferred, genetically-modified cells
2019
Clinical trials that involve genome-edited-cells are growing in popularity, where CAR-T immunotherapy and CRISPR editing are more recognized strategies. Genetic reporters are needed to localize the molecular events that these cells cause in patients. Specifically, a non-immunogenic genetic reporter is urgently needed as current reporters are immunogenic due to derivation from non-human sources. Prostate-specific membrane antigen (PSMA) is potentially non-immunogenic due to its natural, low-level expression in select tissues (self-MHC display). PSMA overexpression on human prostate adenocarcinoma is also visible with certain contrast. We exploit these properties in a transduced, two-component, H uman- D erived, G enetic, P ositron-emitting and F luorescent (HD-GPF) reporter system. Mechanistically analogous to the luciferase/luciferin reporter, PSMA is genetically encoded into non-PSMA expressing 8505C cells and tracked with ACUPA-Cy3-BF3, a single, systemically injected small-...
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