A nanoengineered topical transmucosal cisplatin delivery system induces anti-tumor response in animal models and patients with oral cancer

Manijeh Goldberg, Aaron Manzi, Peter Conway, Stefanie Cantin, Vasudha Mishra, Alka Singh, Alexander T. Pearson, Eric R. Goldberg, Sam Goldberger, Benjamin Flaum, Rifat Hasina, Nyall R. London, Gary L. Gallia, Chetan Bettegowda, Sonya E. O’Neill, Erkin Aydin, Alex Zhavoronkov, Anxo Vidal, Atenea Soto, Maria Jose AlonsoAri J. Rosenberg, Mark W. Lingen, Anil D’Cruz, Nishant Agrawal, Evgeny Izumchenko

Research output: Contribution to journalArticlepeer-review

Abstract

Despite therapeutic advancements, oral cavity squamous cell carcinoma (OCSCC) remains a difficult disease to treat. Systemic platinum-based chemotherapy often leads to dose-limiting toxicity (DLT), affecting quality of life. PRV111 is a nanotechnology-based system for local delivery of cisplatin loaded chitosan particles, that penetrate tumor tissue and lymphatic channels while avoiding systemic circulation and toxicity. Here we evaluate PRV111 using animal models of oral cancer, followed by a clinical trial in patients with OCSCC. In vivo, PRV111 results in elevated cisplatin retention in tumors and negligible systemic levels, compared to the intravenous, intraperitoneal or intratumoral delivery. Furthermore, PRV111 produces robust anti-tumor responses in subcutaneous and orthotopic cancer models and results in complete regression of carcinogen-induced premalignant lesions. In a phase 1/2, open-label, single-arm trial (NCT03502148), primary endpoints of efficacy (≥30% tumor volume reduction) and safety (incidence of DLTs) of neoadjuvant PRV111 were reached, with 69% tumor reduction in ~7 days and over 87% response rate. Secondary endpoints (cisplatin biodistribution, loco-regional control, and technical success) were achieved. No DLTs or drug-related serious adverse events were reported. No locoregional recurrences were evident in 6 months. Integration of PRV111 with current standard of care may improve health outcomes and survival of patients with OCSCC.

Original languageEnglish (US)
Article number4829
JournalNature communications
Volume13
Issue number1
DOIs
StatePublished - Dec 2022

ASJC Scopus subject areas

  • General Chemistry
  • General Biochemistry, Genetics and Molecular Biology
  • General Physics and Astronomy

Fingerprint

Dive into the research topics of 'A nanoengineered topical transmucosal cisplatin delivery system induces anti-tumor response in animal models and patients with oral cancer'. Together they form a unique fingerprint.

Cite this