Vesicular stomatitis virus (VSV) is a potent oncolytic virus for many tumors. VSV that produces interferon-beta (VSV-IFNbeta) is now in early clinical testing for solid tumors. Here, the preclinical activity of VSV and VSV-IFNbeta 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-IFNbeta. VSV-GFP and VSV-IFNbeta were active against NSCLC cells. JAK/STAT inhibition with ruxolitinib re-sensitized resistant H838 cells to VSV-IFNbeta mediated oncolysis. Intratumoral injections of VSV-GFP and VSV-IFNbeta 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-IFNbeta intratumorally. Treatment of LM2 tumors with VSV-IFNbeta resulted in tumor regression, prolonged survival (p < 0.0001), and cure of 30% of mice. Intratumoral injection of VSV-IFNbeta resulted in decreased tumor-infiltrating regulatory T cells (Treg) and increased CD8+ T cells. Tumor cell expression of PDL-1 was increased after VSV-IFNbeta treatment. VSV-IFNbeta has potent antitumor effects and promotes systemic antitumor immunity. These data support further clinical investigation of VSV-IFNbeta for NSCLC.
Patel, M. R., Jacobson, B. A., Ji, Y., Drees, J., Tang, S., Xiong, K., … Kratzke, R. A. (2015). Vesicular stomatitis virus expressing interferon-β is oncolytic and promotes antitumor immune responses in a syngeneic murine model of non-small cell lung cancer. Oncotarget, 6(32). https://doi.org/10.18632/oncotarget.5320