International Journal of Nanomedicine (Jan 2024)

Intratumoral Treatment of Melanoma Tumors with Large Surface Area Microparticle Paclitaxel and Synergy with Immune Checkpoint Inhibition

  • Maulhardt HA,
  • Marin AM,
  • diZerega GS

Journal volume & issue
Vol. Volume 19
pp. 689 – 697

Abstract

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Holly A Maulhardt,1 Alyson M Marin,1 Gere S diZerega1,2 1US Biotest, Inc, San Luis Obispo, CA, USA; 2Nanology, LLC, Fort Worth, TX, USACorrespondence: Gere S diZerega, US Biotest, Inc, 231 Bonetti Drive, Suite 240, San Luis Obispo, CA, 93401, USA, Tel +01 805 595 1300, Email [email protected]: The effects of intratumoral (IT) large surface area microparticle paclitaxel (LSAM-PTX) alone and in combination with systemic administration of the programmed cell death protein antibody (anti-mPD-1) were evaluated in a syngeneic murine model of melanoma. Groups of mice with subcutaneously implanted Clone M3 (Cloudman S91) tumors were treated with single and combination therapies. Tumor volume (TV) measurements, body weights, and clinical observations were followed in-life. At end of study, tumor-site tissues were collected, measured, and processed for flow cytometry along with blood and lymph nodes. The combination of LSAM-PTX + anti-mPD-1 resulted in an antitumoral response, which produced a significant decrease in TV compared to control animals. TV decreases also occurred in the LSAM-PTX and anti-mPD-1 groups. Flow cytometry analysis found increases in granulocytes and M2 macrophages and decreases in dendritic cells (DC) and monocytic myeloid-derived suppressor cells (M-MDSC) in tumor-site tissues. Increases in granulocytes and decreases in CD4+ T cells, macrophages, and M1 macrophages were found in the blood of animals administered the combination treatment. Increases in natural killer (NK) cells were found in lymph node tissue in the combination treatment group. These findings suggest that IT LSAM-PTX may provide benefit in the local treatment of melanomas and may synergize with systemic anti-PD-1 therapy, leading to additional tumoricidal outcomes without added systemic toxicity.Keywords: clone M-3, nanopac, combinatorial immunotherapy, PD-1

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