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

Abstract

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

Acknowledgments

NanoPac^® and NanoDoce^® are registered trademarks of NanOlogy, LLC. The authors would like to thank CritiTech, Inc. for investigational product supply; NanOlogy, LLC. for study funding; and Yazmin Yang for assistance in document preparation.

Disclosure

Holly Maulhardt and Alyson Marin report being full-time employees of US Biotest Inc; Holly Maulhardt and Gere diZerega have a patent 18/154,419 pending to CritiTech Particle Engineering Solutions, LLC; Gere diZerega reports holding a consultant/advisory role, having stock ownership or receiving funding from NanOlogy, LLC.