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

Manijeh Goldberg (), Aaron Manzi, Amritpreet Birdi, Brandon Laporte, 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, Simon Young, Vlad Sandulache, James Melville, Jonathan Shum, Sonya E. O’Neill, Erkin Aydin, Alex Zhavoronkov, Anxo Vidal, Atenea Soto, Maria Jose Alonso, Ari J. Rosenberg, Mark W. Lingen, Anil D’Cruz, Nishant Agrawal () and Evgeny Izumchenko ()
Additional contact information
Manijeh Goldberg: David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology
Aaron Manzi: David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology
Amritpreet Birdi: Privo Technologies
Brandon Laporte: Privo Technologies
Peter Conway: Privo Technologies
Stefanie Cantin: Privo Technologies
Vasudha Mishra: University of Chicago
Alka Singh: University of Chicago
Alexander T. Pearson: University of Chicago
Eric R. Goldberg: Privo Technologies
Sam Goldberger: Privo Technologies
Benjamin Flaum: Privo Technologies
Rifat Hasina: University of Chicago
Nyall R. London: Johns Hopkins University School of Medicine
Gary L. Gallia: Johns Hopkins University School of Medicine
Chetan Bettegowda: Johns Hopkins University School of Medicine
Simon Young: The University of Texas Health Science Center at Houston
Vlad Sandulache: Baylor College of Medicine
James Melville: The University of Texas Health Science Center at Houston
Jonathan Shum: The University of Texas Health Science Center at Houston
Sonya E. O’Neill: Harvard-MIT Division of Health Sciences and Technology, Massachusetts Institute of Technology
Erkin Aydin: David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology
Alex Zhavoronkov: Insilico Medicine
Anxo Vidal: University of Santiago de Compostela
Atenea Soto: University of Santiago de Compostela
Maria Jose Alonso: University of Santiago de Compostela
Ari J. Rosenberg: University of Chicago
Mark W. Lingen: University of Chicago
Anil D’Cruz: Apollo Hospital
Nishant Agrawal: University of Chicago
Evgeny Izumchenko: University of Chicago

Nature Communications, 2022, vol. 13, issue 1, 1-14

Abstract: 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.

Date: 2022
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DOI: 10.1038/s41467-022-31859-3

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