دورية أكاديمية
أعرض في EDS

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

التفاصيل البيبلوغرافية
العنوان: A surgically optimized intraoperative poly(I:C)-releasing hydrogel prevents cancer recurrence.
المؤلفون: Rwandamuriye FX; Telethon Kids Institute, The University of Western Australia, Nedlands, WA, Australia., Evans CW; School of Molecular Sciences, The University of Western Australia, Crawley, WA, Australia., Wylie B; Telethon Kids Institute, The University of Western Australia, Nedlands, WA, Australia., Norret M; School of Molecular Sciences, The University of Western Australia, Crawley, WA, Australia., Vitali B; Telethon Kids Institute, The University of Western Australia, Nedlands, WA, Australia., Ho D; School of Molecular Sciences, The University of Western Australia, Crawley, WA, Australia., Nguyen D; Telethon Kids Institute, The University of Western Australia, Nedlands, WA, Australia., Roper EA; Telethon Kids Institute, The University of Western Australia, Nedlands, WA, Australia., Wang T; Telethon Kids Institute, The University of Western Australia, Nedlands, WA, Australia., Hepburn MS; BRITElab, Harry Perkins Institute of Medical Research, QEII Medical Centre, Nedlands, WA, Australia; Centre for Medical Research, The University of Western Australia, Crawley, WA, Australia; Department of Electrical, Electronic and Computer Engineering, School of Engineering, The University of Western Australia, Crawley, WA, Australia., Sanderson RW; BRITElab, Harry Perkins Institute of Medical Research, QEII Medical Centre, Nedlands, WA, Australia; Centre for Medical Research, The University of Western Australia, Crawley, WA, Australia; Department of Electrical, Electronic and Computer Engineering, School of Engineering, The University of Western Australia, Crawley, WA, Australia., Pfirrmann M; Telethon Kids Institute, The University of Western Australia, Nedlands, WA, Australia; Department of Medical BioSciences, Radboud University Medical Centre, Nijmegen, the Netherlands., Fear VS; Telethon Kids Institute, The University of Western Australia, Nedlands, WA, Australia., Forbes CA; Telethon Kids Institute, The University of Western Australia, Nedlands, WA, Australia., Wyatt K; Perth Veterinary Specialists, Osborne Park, WA, Australia; Murdoch Veterinary School, Murdoch University, Murdoch, WA, Australia., Ryan AL; Telethon Kids Institute, The University of Western Australia, Nedlands, WA, Australia; Department of Oncology, Hematology and Tissue and Cellular Therapies, Perth Children's Hospital, Perth, WA, Australia., Johns TG; Telethon Kids Institute, The University of Western Australia, Nedlands, WA, Australia., Phillips MB; Telethon Kids Institute, The University of Western Australia, Nedlands, WA, Australia; Department of Oncology, Hematology and Tissue and Cellular Therapies, Perth Children's Hospital, Perth, WA, Australia., Hodder R; Department of Surgery, Sir Charles Gairdner Hospital, Nedlands, WA, Australia., Leslie C; Department of Anatomical Pathology, PathWest Laboratory Medicine, QEII Medical Centre, Nedlands, WA, Australia., Kennedy BF; BRITElab, Harry Perkins Institute of Medical Research, QEII Medical Centre, Nedlands, WA, Australia; Centre for Medical Research, The University of Western Australia, Crawley, WA, Australia; Department of Electrical, Electronic and Computer Engineering, School of Engineering, The University of Western Australia, Crawley, WA, Australia., Zemek RM; Telethon Kids Institute, The University of Western Australia, Nedlands, WA, Australia., Iyer KS; School of Molecular Sciences, The University of Western Australia, Crawley, WA, Australia. Electronic address: swaminatha.iyer@uwa.edu.au., Lesterhuis WJ; Telethon Kids Institute, The University of Western Australia, Nedlands, WA, Australia. Electronic address: willem.lesterhuis@uwa.edu.au.
المصدر: Cell reports. Medicine [Cell Rep Med] 2023 Jul 18; Vol. 4 (7), pp. 101113.
نوع المنشور: Journal Article; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: Cell Press Country of Publication: United States NLM ID: 101766894 Publication Model: Print Cited Medium: Internet ISSN: 2666-3791 (Electronic) Linking ISSN: 26663791 NLM ISO Abbreviation: Cell Rep Med Subsets: MEDLINE
أسماء مطبوعة: Original Publication: [Cambridge, MA] : Cell Press, [2020]-
مواضيع طبية MeSH: Hydrogels*/therapeutic use , Neoplasm Recurrence, Local*/prevention & control, Mice ; Animals ; Dogs ; Immunotherapy ; Disease Models, Animal ; Tumor Microenvironment
مستخلص: 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.
Competing Interests: Declaration of interests We declare a patent application pertaining to aspects of this work. B.F.K. discloses a financial interest in OncoRes Medical, a company developing QME for use in surgery. W.J.L. declares consultancy for Douglas Pharmaceuticals and MSD and research funding from Douglas Pharmaceuticals, AstraZeneca, and ENA Therapeutics.
(Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)
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فهرسة مساهمة: Keywords: PD-1; Toll-like receptor; cancer; drug delivery; hydrogel; immunotherapy; poly(I:C); surgical oncology; tumor; wound healing
المشرفين على المادة: 0 (Hydrogels)
تواريخ الأحداث: Date Created: 20230719 Date Completed: 20230721 Latest Revision: 20230804
رمز التحديث: 20230804
مُعرف محوري في PubMed: PMC10394259
DOI: 10.1016/j.xcrm.2023.101113
PMID: 37467718
قاعدة البيانات: MEDLINE
الوصف
تدمد:2666-3791
DOI:10.1016/j.xcrm.2023.101113