| Summary: | Intratumoral (IT) administration of submicron particle docetaxel (NanoDoce<sup>®</sup>, NanOlogy LLC, Fort Worth, TX, USA) and its efficacy against genitourinary-oncologic xenografts in rats and mice, xenograft-site docetaxel concentrations and immune-cell infiltration were studied. IT-NanoDoce<sup>®</sup>, IV-docetaxel and IT-vehicle were administered to clear cell renal carcinoma (786-O: rats), transitional cell bladder carcinoma (UM-UC-3: mice) and prostate carcinoma (PC-3: mice). Treatments were given every 7 days with 1, 2, or 3 doses administered. Animals were followed for tumor growth and clinical signs. At necropsy, 786-O and UM-UC-3 tumor-site tissues were evaluated by H&E and IHC and analyzed by LC-MS/MS for docetaxel concentration. Two and 3 cycles of IT-NanoDoce<sup>®</sup> significantly reduced UM-UC-3 tumor volume (<i>p</i> < 0.01) and eliminated most UM-UC-3 and 786-O tumors. In both models, NanoDoce<sup>®</sup> treatment was associated with (peri)tumor-infiltrating immune cells. Lymphoid structures were observed in IT-NanoDoce<sup>®</sup>-treated UM-UC-3 animals adjacent to tumor sites. IT-vehicle and IV-docetaxel exhibited limited immune-cell infiltration. In both studies, high levels of docetaxel were detected in NanoDoce<sup>®</sup>-treated animals up to 50 days post-treatment. In the PC-3 study, IT-NanoDoce<sup>®</sup> and IV-docetaxel resulted in similar tumor reduction. NanoDoce<sup>®</sup> significantly reduced tumor volume compared to IT-vehicle in all xenografts (<i>p</i> < 0.0001). We hypothesize that local, persistent, therapeutic levels of docetaxel from IT-NanoDoce<sup>®</sup> reduces tumor burden while increasing immune-cell infiltration. IT NanoDoce<sup>®</sup> treatment of prostate, renal and bladder cancer may result in enhanced tumoricidal effects.
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