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

1
US Biotest, Inc., 231 Bonetti Drive, Suite 240, San Luis Obispo, CA 93401, USA
2
Western Diagnostic Services Laboratory, 1414 East Main Street, Suite 102, Santa Maria, CA 93454, USA
3
Department of Medicine, The University of Southern California Norris Cancer Center, 1441 Eastlake Avenue, Los Angeles, CA 90033, USA
4
Department of Urology, University of Texas MD Anderson Cancer Center, 1515 Pressler, Unit 1373, Houston, TX 77030, USA
5
NanOlogy, LLC., 3909 Hulen Street, Fort Worth, TX 76107, USA
*
Author to whom correspondence should be addressed.
Cancers 2019, 11(4), 577; https://doi.org/10.3390/cancers11040577
Received: 28 March 2019 / Revised: 19 April 2019 / Accepted: 22 April 2019 / Published: 24 April 2019
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Abstract

Intratumoral (IT) administration of submicron particle docetaxel (NanoDoce®, 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®, 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® significantly reduced UM-UC-3 tumor volume (p < 0.01) and eliminated most UM-UC-3 and 786-O tumors. In both models, NanoDoce® treatment was associated with (peri)tumor-infiltrating immune cells. Lymphoid structures were observed in IT-NanoDoce®-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®-treated animals up to 50 days post-treatment. In the PC-3 study, IT-NanoDoce® and IV-docetaxel resulted in similar tumor reduction. NanoDoce® significantly reduced tumor volume compared to IT-vehicle in all xenografts (p < 0.0001). We hypothesize that local, persistent, therapeutic levels of docetaxel from IT-NanoDoce® reduces tumor burden while increasing immune-cell infiltration. IT NanoDoce® treatment of prostate, renal and bladder cancer may result in enhanced tumoricidal effects. View Full-Text
Keywords: docetaxel; NanoDoce®; intratumoral; nanoparticle; genitourinary oncology; cancer; bladder; renal; prostate docetaxel; NanoDoce®; intratumoral; nanoparticle; genitourinary oncology; cancer; bladder; renal; prostate
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Maulhardt, H.A.; Hylle, L.; Frost, M.V.; Tornio, A.; Dafoe, S.; Drummond, L.; Quinn, D.I.; Kamat, A.M.; diZerega, G.S. Local Injection of Submicron Particle Docetaxel is Associated with Tumor Eradication, Reduced Systemic Toxicity and an Immunologic Response in Uro-Oncologic Xenografts. Cancers 2019, 11, 577.

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