Vesicular stomatitis virus expressing interferon-β is oncolytic and promotes antitumor immune responses in a syngeneic murine model of non-small cell lung cancer

Abstract

Vesicular stomatitis virus (VSV) is a potent oncolytic virus for many tumors. VSV that produces interferon-β (VSV-IFNβ) is now in early clinical testing for solid tumors. Here, the preclinical activity of VSV and VSV-IFNβ against non-small cell lung cancer (NSCLC) is reported. NSCLC cell lines were treated in vitro with VSV expressing green fluorescence protein (VSV-GFP) and VSV-IFNβ. VSV-GFP and VSV-IFNβ were active against NSCLC cells. JAK/STAT inhibition with ruxolitinib re-sensitized resistant H838 cells to VSV-IFNβ mediated oncolysis. Intratumoral injections of VSV-GFP and VSV-IFNβ reduced tumor growth and weight in H2009 nude mouse xenografts (p < 0.01). A similar trend was observed in A549 xenografts. Syngeneic LM2 lung tumors grown in flanks of A/J mice were injected with VSV-IFNβ intratumorally. Treatment of LM2 tumors with VSV-IFNβ resulted in tumor regression, prolonged survival (p < 0.0001), and cure of 30% of mice. Intratumoral injection of VSV-IFNβ resulted in decreased tumor-infiltrating regulatory T cells (Treg) and increased CD8+ T cells. Tumor cell expression of PDL-1 was increased after VSV-IFNβ treatment. VSV-IFNβ has potent antitumor effects and promotes systemic antitumor immunity. These data support further clinical investigation of VSV-IFNβ for NSCLC.

Oncolytic Vesicular Stomatitis Virus as a Viro-Immunotherapy: Defeating Cancer with a “Hammer” and “Anvil”

“…Improved safety of rVSV-mIFN-β was also confirmed in this study [106]. Along similar lines, rVSV-IFN-β was shown to induce a systemic antitumor immune response, marked by increased CD8 + tumor-infiltrating lymphocytes (TILs) and decreased Tregs and mMDSCs, in both injected and non-injected tumors, in a model of non-small cell lung cancer [107]. Furthermore, there was evidence of the onset of a memory immune response shown via rechallenge experiments in the same study [107].…”

Recent advances in vesicular stomatitis virus-based oncolytic virotherapy: a 5-year update

“…Using VSVs encoding type I and type III IFNs Several recent pre-clinical studies have shown that VSVIFNb and VSV-IFNb-NIS (additionally expresses the NIS to track virus spread) are oncoselective and safe in a variety of tumour and animal models [24,[27][28][29][30][31]. Although mice and rats continue to serve as the most commonly used animal models for VSV-based OV therapy, a recent study evaluated the safety of intravenously administered VSV-IFNb-NIS in purpose-bred beagle dogs.…”

“…Another common approach is to use VSV-encoding IFNb (VSV-IFNb), which oncoselectivity is based on virus-encoded IFNb expression that stimulates an innate immune response in normal cells but not in type I IFN defective cancer cells [22,23]. IFNb also stimulates tumour-specific immunity [24]. VSV-IFNb showed no signs of neurotoxicity at any time point in rhesus macaques when administered via intrahepatic injection [22].…”

The importance of programmed death ligand 1 gene expression, epidermal growth factor receptor gene mutations and serum epidermal growth factor receptor levels in Turkish non-small cell lung cancer patients

“…[14] Moreover, Aguiar et al [16] showed that nivolumab (inhibited PD-1 and PD-L1) treatment had different bioavailability and outcomes in PD-L1 negative and positive cases. Furthermore, although Patel et al [17] investigated vesicular stomatitis virus (VSV), they also reported positive results related to anti-tumor effect and tumor immunity due to increased PD-L1 expression after the interferon-b treatment.…”