Journal
ONCOTARGET
Volume 6, Issue 32, Pages 33165-33177Publisher
IMPACT JOURNALS LLC
DOI: 10.18632/oncotarget.5320
Keywords
oncolytic virus; NSCLC; interferon-beta; VSV; Treg
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Funding
- NIH [5 T32 HL07062]
- Breath of Hope Foundation Research Fellowship
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Vesicular stomatitis virus (VSV) is a potent oncolytic virus for many tumors. VSV that produces interferon-beta (VSV-IFN beta) is now in early clinical testing for solid tumors. Here, the preclinical activity of VSV and VSV-IFN beta 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-IFN beta. VSV-GFP and VSV-IFN beta were active against NSCLC cells. JAK/STAT inhibition with ruxolitinib re-sensitized resistant H838 cells to VSV-IFN beta mediated oncolysis. Intratumoral injections of VSV-GFP and VSV-IFN beta 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-IFN beta intratumorally. Treatment of LM2 tumors with VSV-IFN beta resulted in tumor regression, prolonged survival (p < 0.0001), and cure of 30% of mice. Intratumoral injection of VSV-IFN beta resulted in decreased tumor-infiltrating regulatory T cells (Treg) and increased CD8+ T cells. Tumor cell expression of PDL-1 was increased after VSV-IFN beta treatment. VSV-IFN beta has potent antitumor effects and promotes systemic antitumor immunity. These data support further clinical investigation of VSV-IFN beta for NSCLC.
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