A surgically optimized intraoperative poly(I:C)-releasing hydrogel prevents cancer recurrence

Francois Xavier Rwandamuriye, Cameron W. Evans, Ben Wylie, Marck Norret, Breana Vitali, Diwei Ho, Dat Nguyen, Ellise A. Roper, Tao Wang, Matt S. Hepburn, Rowan W. Sanderson, Maren Pfirrmann, Vanessa S. Fear, Catherine A. Forbes, Ken Wyatt, Anne L. Ryan, Terrance G. Johns, Marianne B. Phillips, Rupert Hodder, Connull LeslieBrendan F. Kennedy, Rachael M. Zemek, Killugudi Swaminathan Iyer, Willem Joost Lesterhuis

Research output: Contribution to journalArticlepeer-review

2 Citations (Scopus)

Abstract

Recurrences frequently occur following surgical removal of primary tumors. In many cancers, adjuvant therapies have limited efficacy. Surgery provides access to the tumor microenvironment, creating an opportunity for local therapy, in particular immunotherapy, which can induce local and systemic anti-cancer effects. Here, we develop a surgically optimized biodegradable hyaluronic acid-based hydrogel for sustained intraoperative delivery of Toll-like receptor 3 agonist poly(I:C) and demonstrate that it significantly reduces tumor recurrence after surgery in multiple mouse models. Mechanistically, poly(I:C) induces a transient interferon alpha (IFNα) response, reshaping the tumor/wound microenvironment by attracting inflammatory monocytes and depleting regulatory T cells. We demonstrate that a pre-existing IFN signature predicts response to the poly(I:C) hydrogel, which sensitizes tumors to immune checkpoint therapy. The safety, immunogenicity, and surgical feasibility are confirmed in a veterinary trial in canine soft tissue tumors. The surgically optimized poly(I:C)-loaded hydrogel provides a safe and effective approach to prevent cancer recurrence.

Original languageEnglish
Article number101113
JournalCell Reports Medicine
Volume4
Issue number7
DOIs
Publication statusPublished - 18 Jul 2023

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