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 Leslie; Brendan F. Kennedy; Rachael M. Zemek; Killugudi Swaminathan Iyer; Willem Joost Lesterhuis

doi:10.1016/j.xcrm.2023.101113

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

Journal article

Open access

Peer reviewed

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, …

Cell reports. Medicine, Vol.4(7), 101113

2023

DOI: https://doi.org/10.1016/j.xcrm.2023.101113

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Abstract

cancer

drug delivery

hydrogel

immunotherapy

PD-1

poly(I:C)

surgical oncology

Toll-like receptor

tumor

wound healing

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. [Display omitted]

Details

Title: A surgically optimized intraoperative poly(I:C)-releasing hydrogel prevents cancer recurrence
Authors/Creators: Francois Xavier Rwandamuriye - Telethon Kids Institute, The University of Western Australia, Nedlands, WA, Australia
Cameron W. Evans - School of Molecular Sciences, The University of Western Australia, Crawley, WA, Australia
Ben Wylie - Telethon Kids Institute, The University of Western Australia, Nedlands, WA, Australia
Marck Norret - School of Molecular Sciences, The University of Western Australia, Crawley, WA, Australia
Breana Vitali - Telethon Kids Institute, The University of Western Australia, Nedlands, WA, Australia
Diwei Ho - School of Molecular Sciences, The University of Western Australia, Crawley, WA, Australia
Dat Nguyen - Telethon Kids Institute, The University of Western Australia, Nedlands, WA, Australia
Ellise A. Roper - Telethon Kids Institute, The University of Western Australia, Nedlands, WA, Australia
Tao Wang - Zhengzhou University
Matt S. Hepburn - Harry Perkins Institute of Medical Research
Rowan W. Sanderson - Harry Perkins Institute of Medical Research
Maren Pfirrmann - Telethon Kids Institute, The University of Western Australia, Nedlands, WA, Australia
Vanessa S. Fear - Telethon Kids Institute, The University of Western Australia, Nedlands, WA, Australia
Catherine A. Forbes - Telethon Kids Institute, The University of Western Australia, Nedlands, WA, Australia
Ken Wyatt - Perth Veterinary Specialists, Osborne Park, WA, Australia
Anne L. Ryan - Telethon Kids Institute, The University of Western Australia, Nedlands, WA, Australia
Terrance G. Johns - Telethon Kids Institute, The University of Western Australia, Nedlands, WA, Australia
Marianne B. Phillips - Telethon Kids Institute, The University of Western Australia, Nedlands, WA, Australia
Rupert Hodder - Sir Charles Gairdner Hospital
Connull Leslie - Pathwest Laboratory Medicine
Brendan F. Kennedy - Harry Perkins Institute of Medical Research
Rachael M. Zemek - Telethon Kids Institute, The University of Western Australia, Nedlands, WA, Australia
Killugudi Swaminathan Iyer - School of Molecular Sciences, The University of Western Australia, Crawley, WA, Australia
Willem Joost Lesterhuis - Telethon Kids Institute, The University of Western Australia, Nedlands, WA, Australia
Publication Details: Cell reports. Medicine, Vol.4(7), 101113
Publisher: Elsevier Inc
Identifiers: 991005593758907891
Murdoch Affiliation: School of Veterinary Medicine
Language: English
Resource Type: Journal article

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Collaboration types: Domestic collaboration; International collaboration
Citation topics: 1 Clinical & Life Sciences; 1.6 Immunology; 1.6.214 Checkpoint Inhibition
Web Of Science research areas: Cell Biology; Medicine, Research & Experimental
ESI research areas: Clinical Medicine