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

  • Patel M
  • Jacobson B
  • Ji Y
  • et al.
N/ACitations
Citations of this article
31Readers
Mendeley users who have this article in their library.

Abstract

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.

Cite

CITATION STYLE

APA

Patel, M. R., Jacobson, B. A., Ji, Y., Drees, J., Tang, S., Xiong, K., … Kratzke, R. A. (2015). Vesicular stomatitis virus expressing interferon-&#x3B2; 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

Register to see more suggestions

Mendeley helps you to discover research relevant for your work.

Already have an account?

Save time finding and organizing research with Mendeley

Sign up for free