Local Injection of Submicron Particle Docetaxel is Associated with Tumor Eradication, Reduced Systemic Toxicity and an Immunologic Response in Uro-Oncologic Xenografts

• Main Authors: Holly A. Maulhardt, Lauren Hylle, Michael V. Frost, Ashley Tornio, Sara Dafoe, Leanne Drummond, David I. Quinn, Ashish M. Kamat, Gere S. diZerega
• Format: Article
• Language: English
• Published: MDPI AG 2019-04-01
• Series: Cancers
• Subjects: docetaxel; NanoDoce^®; intratumoral; nanoparticle; genitourinary oncology; cancer; bladder; renal; prostate
• Online Access: https://www.mdpi.com/2072-6694/11/4/577

Intratumoral (IT) administration of submicron particle docetaxel (NanoDoce^&#174;, 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^&#174;, 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&amp;E and IHC and analyzed by LC-MS/MS for docetaxel concentration. Two and 3 cycles of IT-NanoDoce^&#174; significantly reduced UM-UC-3 tumor volume (<i>p</i> &lt; 0.01) and eliminated most UM-UC-3 and 786-O tumors. In both models, NanoDoce^&#174; treatment was associated with (peri)tumor-infiltrating immune cells. Lymphoid structures were observed in IT-NanoDoce^&#174;-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^&#174;-treated animals up to 50 days post-treatment. In the PC-3 study, IT-NanoDoce^&#174; and IV-docetaxel resulted in similar tumor reduction. NanoDoce^&#174; significantly reduced tumor volume compared to IT-vehicle in all xenografts (<i>p</i> &lt; 0.0001). We hypothesize that local, persistent, therapeutic levels of docetaxel from IT-NanoDoce^&#174; reduces tumor burden while increasing immune-cell infiltration. IT NanoDoce^&#174; treatment of prostate, renal and bladder cancer may result in enhanced tumoricidal effects.