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- Title
Vanadyl sulfate-enhanced oncolytic virus immunotherapy mediates the antitumor immune response by upregulating the secretion of pro-inflammatory cytokines and chemokines.
- Authors
Alluqmani, Nouf; Jirovec, Anna; Taha, Zaid; Varette, Oliver; Chen, Andrew; Serrano, Daniel; Maznyi, Glib; Khan, Sarwat; Forbes, Nicole E.; Arulanandam, Rozanne; Auer, Rebecca C.; Diallo, Jean-Simon
- Abstract
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 RNAbased OVs such as oncolytic vesicular stomatitis virus (VSV🜂51), 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+VSV🜂51 combination therapy to understand the immunological mechanism of action leading to improved antitumor responses. VS+VSV🜂51 combination therapy significantly increased the levels of IFN-γ and IL-6, and improved tumor antigenspecific 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 VSVD51 in combination with VS further improved therapeutic outcomes in a syngeneic CT26WT colon cancer model.
- Publication
Frontiers in Immunology, 2022, Vol 13, p1
- ISSN
1664-3224
- Publication type
Article
- DOI
10.3389/fimmu.2022.1032356