Vanadyl sulfate-enhanced oncolytic virus immunotherapy mediates the antitumor immune response by upregulating the secretion of pro-inflammatory cytokines and chemokines.

Autor:	Alluqmani N; Centre for Innovative Cancer Research, Ottawa Hospital Research Institute, Ottawa, ON, Canada.; Department of Biochemistry, Microbiology and Immunology, Faculty of Medicine, University of Ottawa, ON, Canada.; Research Center, Molecular Oncology Department King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia., Jirovec A; Centre for Innovative Cancer Research, Ottawa Hospital Research Institute, Ottawa, ON, Canada.; Department of Biochemistry, Microbiology and Immunology, Faculty of Medicine, University of Ottawa, ON, Canada., Taha Z; Centre for Innovative Cancer Research, Ottawa Hospital Research Institute, Ottawa, ON, Canada.; Department of Biochemistry, Microbiology and Immunology, Faculty of Medicine, University of Ottawa, ON, Canada., Varette O; Centre for Innovative Cancer Research, Ottawa Hospital Research Institute, Ottawa, ON, Canada., Chen A; Centre for Innovative Cancer Research, Ottawa Hospital Research Institute, Ottawa, ON, Canada., Serrano D; Centre for Innovative Cancer Research, Ottawa Hospital Research Institute, Ottawa, ON, Canada., Maznyi G; Centre for Innovative Cancer Research, Ottawa Hospital Research Institute, Ottawa, ON, Canada., Khan S; Centre for Innovative Cancer Research, Ottawa Hospital Research Institute, Ottawa, ON, Canada., Forbes NE; Centre for Innovative Cancer Research, Ottawa Hospital Research Institute, Ottawa, ON, Canada., Arulanandam R; Centre for Innovative Cancer Research, Ottawa Hospital Research Institute, Ottawa, ON, Canada., Auer RC; Centre for Innovative Cancer Research, Ottawa Hospital Research Institute, Ottawa, ON, Canada.; Department of Surgery, University of Ottawa, Ottawa, ON, Canada., Diallo JS; Centre for Innovative Cancer Research, Ottawa Hospital Research Institute, Ottawa, ON, Canada.; Department of Biochemistry, Microbiology and Immunology, Faculty of Medicine, University of Ottawa, ON, Canada.
Jazyk:	angličtina
Zdroj:	Frontiers in immunology [Front Immunol] 2022 Nov 28; Vol. 13, pp. 1032356. Date of Electronic Publication: 2022 Nov 28 (Print Publication: 2022).
DOI:	10.3389/fimmu.2022.1032356
Abstrakt:	Oncolytic viruses (OVs) are promising anticancer treatments that specifically replicate in and kill cancer cells and have profound immunostimulatory effects. We previously reported the potential of vanadium-based compounds such as vanadyl sulfate (VS) as immunostimulatory enhancers of OV immunotherapy. These compounds, in conjunction with RNA-based OVs such as oncolytic vesicular stomatitis virus (VSVΔ51), improve viral spread and oncolysis, leading to long-term antitumor immunity and prolonged survival in resistant tumor models. This effect is associated with a virus-induced antiviral type I IFN response shifting towards a type II IFN response in the presence of vanadium. Here, we investigated the systemic impact of VS+VSVΔ51 combination therapy to understand the immunological mechanism of action leading to improved antitumor responses. VS+VSVΔ51 combination therapy significantly increased the levels of IFN-γ and IL-6, and improved tumor antigen-specific T-cell responses. Supported by immunological profiling and as a proof of concept for the design of more effective therapeutic regimens, we found that local delivery of IL-12 using VSVΔ51 in combination with VS further improved therapeutic outcomes in a syngeneic CT26WT colon cancer model. Competing Interests: J-SD is co-inventor on a patent covering the use of vanadium compounds as enhancers of RNA viruses and holds shares in Virica Biotech and Virano Therapeutics that hold licenses to this intellectual property. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2022 Alluqmani, Jirovec, Taha, Varette, Chen, Serrano, Maznyi, Khan, Forbes, Arulanandam, Auer and Diallo.)
Databáze:	MEDLINE
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