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Octyl itaconate enhances VSVΔ51 oncolytic virotherapy by multitarget inhibition of antiviral and inflammatory pathways.
Kurmasheva, Naziia; Said, Aida; Wong, Boaz; Kinderman, Priscilla; Han, Xiaoying; Rahimic, Anna H F; Kress, Alena; Carter-Timofte, Madalina E; Holm, Emilia; van der Horst, Demi; Kollmann, Christoph F; Liu, Zhenlong; Wang, Chen; Hoang, Huy-Dung; Kovalenko, Elina; Chrysopoulou, Maria; Twayana, Krishna Sundar; Ottosen, Rasmus N; Svenningsen, Esben B; Begnini, Fabio; Kiib, Anders E; Kromm, Florian E H; Weiss, Hauke J; Di Carlo, Daniele; Muscolini, Michela; Higgins, Maureen; van der Heijden, Mirte; Bardoul, Angelina; Tong, Tong; Ozsvar, Attila; Hou, Wen-Hsien; Schack, Vivien R; Holm, Christian K; Zheng, Yunan; Ruzek, Melanie; Kalucka, Joanna; de la Vega, Laureano; Elgaher, Walid A M; Korshoej, Anders R; Lin, Rongtuan; Hiscott, John; Poulsen, Thomas B; O'Neill, Luke A; Roy, Dominic G; Rinschen, Markus M; van Montfoort, Nadine; Diallo, Jean-Simon; Farin, Henner F; Alain, Tommy; Olagnier, David.
Affiliation
  • Kurmasheva N; Department of Biomedicine, Aarhus University, 8000, Aarhus C, Denmark.
  • Said A; Department of Biochemistry Microbiology and Immunology, University of Ottawa, Ottawa, ON, K1H 8M5, Canada.
  • Wong B; Children's Hospital of Eastern Ontario Research Institute, Ottawa, ON, K1H 8L1, Canada.
  • Kinderman P; Department of Biochemistry Microbiology and Immunology, University of Ottawa, Ottawa, ON, K1H 8M5, Canada.
  • Han X; Ottawa Hospital Research Insitute, Ottawa, ON, K1H 8L6, Canada.
  • Rahimic AHF; Department of Gastroenterology and Hepatology, Leiden University Medical Center, Leiden, The Netherlands.
  • Kress A; Lady Davis Institute, Jewish General Hospital and Department of Medicine, McGill University, Montreal, QC, H3T 1E2, Canada.
  • Carter-Timofte ME; Department of Biomedicine, Aarhus University, 8000, Aarhus C, Denmark.
  • Holm E; Georg-Speyer-Haus, Institute for Tumor Biology and Experimental Therapy, Frankfurt am Main, Germany.
  • van der Horst D; Frankfurt Cancer Institute, Goethe University, Frankfurt am Main, Germany.
  • Kollmann CF; Faculty of Biological Sciences, Goethe University, 60438, Frankfurt am Main, Germany.
  • Liu Z; Department of Biomedicine, Aarhus University, 8000, Aarhus C, Denmark.
  • Wang C; Department of Biomedicine, Aarhus University, 8000, Aarhus C, Denmark.
  • Hoang HD; Department of Biomedicine, Aarhus University, 8000, Aarhus C, Denmark.
  • Kovalenko E; Department of Biomedicine, Aarhus University, 8000, Aarhus C, Denmark.
  • Chrysopoulou M; Lady Davis Institute, Jewish General Hospital and Department of Medicine, McGill University, Montreal, QC, H3T 1E2, Canada.
  • Twayana KS; Lady Davis Institute, Jewish General Hospital and Department of Medicine, McGill University, Montreal, QC, H3T 1E2, Canada.
  • Ottosen RN; Department of Biochemistry Microbiology and Immunology, University of Ottawa, Ottawa, ON, K1H 8M5, Canada.
  • Svenningsen EB; Children's Hospital of Eastern Ontario Research Institute, Ottawa, ON, K1H 8L1, Canada.
  • Begnini F; Department of Biomedicine, Aarhus University, 8000, Aarhus C, Denmark.
  • Kiib AE; Department of Biomedicine, Aarhus University, 8000, Aarhus C, Denmark.
  • Kromm FEH; Department of Biomedicine, Aarhus University, 8000, Aarhus C, Denmark.
  • Weiss HJ; Department of Chemistry, Aarhus University, 8000, Aarhus C, Denmark.
  • Di Carlo D; Department of Chemistry, Aarhus University, 8000, Aarhus C, Denmark.
  • Muscolini M; Department of Chemistry, Aarhus University, 8000, Aarhus C, Denmark.
  • Higgins M; Department of Chemistry, Aarhus University, 8000, Aarhus C, Denmark.
  • van der Heijden M; Department of Chemistry, Aarhus University, 8000, Aarhus C, Denmark.
  • Bardoul A; School of Biochemistry and Immunology, Trinity College Dublin, Trinity Biomedical Sciences Institute, Dublin 2, Ireland.
  • Tong T; Pasteur Laboratories, Istituto Pasteur Italia - Fondazione Cenci Bolognetti, Rome, 00161, Italy.
  • Ozsvar A; Pasteur Laboratories, Istituto Pasteur Italia - Fondazione Cenci Bolognetti, Rome, 00161, Italy.
  • Hou WH; Jacqui Wood Cancer Centre, Division of Cellular Medicine, School of Medicine, University of Dundee, Dundee, UK.
  • Schack VR; Department of Gastroenterology and Hepatology, Leiden University Medical Center, Leiden, The Netherlands.
  • Holm CK; Cancer Axis, CHUM Research Centre, Montreal, Canada.
  • Zheng Y; Department of Microbiology, Infectious Diseases and Immunology, Faculty of Medicine, University of Montreal, Montreal, Canada.
  • Ruzek M; Institut du Cancer de Montréal, Montreal, QC, Canada.
  • Kalucka J; Department of Neurosurgery, Aarhus University Hospital, 8200, Aarhus N, Denmark.
  • de la Vega L; Department of Clinical Medicine, Aarhus University, 8200, Aarhus N, Denmark.
  • Elgaher WAM; DCCC Brain Tumor Center, Copenhagen University Hospital, Copenhagen, Denmark.
  • Korshoej AR; Department of Biomedicine, Aarhus University, 8000, Aarhus C, Denmark.
  • Lin R; Department of Clinical Medicine, Aarhus University, 8200, Aarhus N, Denmark.
  • Hiscott J; Department of Biomedicine, Aarhus University, 8000, Aarhus C, Denmark.
  • Poulsen TB; Department of Biomedicine, Aarhus University, 8000, Aarhus C, Denmark.
  • O'Neill LA; Department of Biomedicine, Aarhus University, 8000, Aarhus C, Denmark.
  • Roy DG; Small Molecule Therapeutics & Platform Technologies, AbbVie Inc., 1 North Waukegon Road, North Chicago, IL, 60064, USA.
  • Rinschen MM; AbbVie, Bioresearch Center, 100 Research Drive, Worcester, MA, 01608, USA.
  • van Montfoort N; Department of Biomedicine, Aarhus University, 8000, Aarhus C, Denmark.
  • Diallo JS; Steno Diabetes Center Aarhus, Aarhus University Hospital, Aarhus, Denmark.
  • Farin HF; Jacqui Wood Cancer Centre, Division of Cellular Medicine, School of Medicine, University of Dundee, Dundee, UK.
  • Alain T; Department of Drug Design and Optimization, Helmholtz Institute for Pharmaceutical Research Saarland (HIPS), Helmholtz Centre for Infection Research (HZI), Saarland University, E8.1, 66123, Saarbrücken, Germany.
  • Olagnier D; Department of Neurosurgery, Aarhus University Hospital, 8200, Aarhus N, Denmark.
Nat Commun ; 15(1): 4096, 2024 May 15.
Article in En | MEDLINE | ID: mdl-38750019
ABSTRACT
The presence of heterogeneity in responses to oncolytic virotherapy poses a barrier to clinical effectiveness, as resistance to this treatment can occur through the inhibition of viral spread within the tumor, potentially leading to treatment failures. Here we show that 4-octyl itaconate (4-OI), a chemical derivative of the Krebs cycle-derived metabolite itaconate, enhances oncolytic virotherapy with VSVΔ51 in various models including human and murine resistant cancer cell lines, three-dimensional (3D) patient-derived colon tumoroids and organotypic brain tumor slices. Furthermore, 4-OI in combination with VSVΔ51 improves therapeutic outcomes in a resistant murine colon tumor model. Mechanistically, we find that 4-OI suppresses antiviral immunity in cancer cells through the modification of cysteine residues in MAVS and IKKß independently of the NRF2/KEAP1 axis. We propose that the combination of a metabolite-derived drug with an oncolytic virus agent can greatly improve anticancer therapeutic outcomes by direct interference with the type I IFN and NF-κB-mediated antiviral responses.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Succinates / Oncolytic Viruses / Oncolytic Virotherapy Limits: Animals / Female / Humans Language: En Journal: Nat Commun Journal subject: BIOLOGIA / CIENCIA Year: 2024 Document type: Article Affiliation country: Denmark
Fulltext
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Succinates / Oncolytic Viruses / Oncolytic Virotherapy Limits: Animals / Female / Humans Language: En Journal: Nat Commun Journal subject: BIOLOGIA / CIENCIA Year: 2024 Document type: Article Affiliation country: Denmark