Click therapy is a new therapeutic strategy for cancers minimizing systemic toxicity and enhancing therapeutic efficacy. For this strategy, slow internalization of pretargeted cell surface receptors gives a sufficient window for clearance of the unbound pretargeting component before administration of delivery components. Here, we tested click therapy in PSMA(+) PC3-PIP and PSMA(-) PC3-Flu (control) tumors to evaluate delivery and internalization of components. We observed that internalization of 5D3 antibody is fast, which may interfere with the delivery of therapeutic components. In large tumors with leaky vasculature, 5D3 antibody can effectively extravasate leading to the cluster formation with delivery component in tumor microenvironment.
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