Vesicular stomatitis virus expressing interferon-β is oncolytic and promotes antitumor immune responses in a syngeneic murine model of non-small cell lung cancer
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Manish R. Patel1, Blake A. Jacobson1, Yan Ji1, Jeremy Drees2, Shaogeng Tang1, Kerry Xiong1, Hengbing Wang1, Jennifer E. Prigge1, Alexander S. Dash1, Andrea K. Kratzke1, Emily Mesev1, Ryan Etchison1, Mark J. Federspiel3, Stephen J. Russell3, Robert A. Kratzke1
1Department of Medicine, Division of Hematology, Oncology, and Transplantation, University of Minnesota Medical School, Minneapolis, MN, USA
2Department of Surgery, University of Minnesota Medical School, Minneapolis, MN, USA
3Mayo Clinic, Department of Molecular Medicine, Rochester, MN, USA
Manish R. Patel, e-mail: [email protected]
Keywords: oncolytic virus, NSCLC, interferon-β, VSV, Treg
Received: April 28, 2015 Accepted: September 16, 2015 Published: September 28, 2015
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.
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