Intratumoral submicron particle docetaxel inhibits syngeneic Renca renal cancer growth and increases CD4+, CD8+, and Tre
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SHORT REPORT
Intratumoral submicron particle docetaxel inhibits syngeneic Renca renal cancer growth and increases CD4+, CD8+, and Treg levels in peripheral blood Holly A. Maulhardt 1 & Alyson M. Marin 1 & Gere S. diZerega 1,2 Received: 17 January 2020 / Accepted: 9 March 2020 # The Author(s) 2020
Summary Administration of chemotherapeutics as direct injections into tumors offers increased anti-tumor activity and reduced systemic toxicity. In this study, the Renca syngeneic murine xenograft model of renal cancer was used to evaluate the effects of intratumoral (IT) submicron particle docetaxel (NanoDoce®) on tumor growth and immunomodulation. Tumor volume (TV) was compared to controls, including intravenous (IV) chemotherapy. Flow cytometry of peripheral bloods and tumors was used to evaluate immune cell populations. Groups of animals were inoculated with a second Renca tumor at a site distant from the primary tumor. IT NanoDoce significantly reduced primary TV and reduced the growth rates of untreated secondary tumors. CD4+, CD8+ and Treg populations were increased in peripheral bloods from animals administered IT NanoDoce. Additional evaluation of the effect of IT NanoDoce on peripheral and local immune cell populations as well as the impact on sites of distant tumor growth are warranted. Keywords Intratumoral . Docetaxel . NanoDoce . Renal carcinoma . Renca
Introduction Previously, we found that submicron particles of docetaxel (NanoDoce®) injected into UM-UC-3 and 786-O xenograft tumors in rodents significantly inhibited or eradicated the tumor as well as stimulated an immune cell infiltrate into the tumor. In the same models, similar reductions in tumor volume and immune cell infiltration into the tumor did not occur following IV docetaxel treatment. Evaluation of tumor tissues from these animals determined that IT NanoDoce administration resulted in high levels (> 1500 μg/g of tissue) of docetaxel within the tumor up to 50 days after treatment [1]. Further, we found that nebulized submicron particle paclitaxel (NanoPac®) substantially reduced or eradicated Calu-3 non-small cell lung cancer (NSCLC) tumors in immunocompromised
* Gere S. diZerega [email protected] 1
US Biotest, Inc., 231 Bonetti Drive, Suite 240, San Luis Obispo, CA 93401, USA
2
NanOlogy, LLC., 3909 Hulen Street, Fort Worth, TX 76107, USA
mice which did not occur following IV administration of nab-paclitaxel [2, 3]. These previous studies were performed in rodents with genetically depleted T cells, whereas here we evaluated the response of an intact immune system to direct injection of NanoDoce compared to IV docetaxel in a Renca syngeneic model. This report describes preliminary evaluation of efficacy, toxicity and immunomodulation in a syngeneic mouse model when NanoDoce is administered directly to a primary renal cell carcinoma. The effects on an untreated secondary tumor implanted at a site distant from the treated primary tumor are explored. Tumor growth inhibition following IT injection of NanoDoce is compared to IT vehicl
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