title: 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.
authors.affiliation: Department of Medicine, Division of Hematology, Oncology, and Transplantation, University of Minnesota Medical School, Minneapolis, MN, USA.
authors.forename: Manish R
authors.initials: MR
authors.lastname: Patel
authors.affiliation: Department of Medicine, Division of Hematology, Oncology, and Transplantation, University of Minnesota Medical School, Minneapolis, MN, USA.
authors.forename: Blake A
authors.initials: BA
authors.lastname: Jacobson
authors.affiliation: Department of Medicine, Division of Hematology, Oncology, and Transplantation, University of Minnesota Medical School, Minneapolis, MN, USA.
authors.forename: Yan
authors.initials: Y
authors.lastname: Ji
authors.affiliation: Department of Surgery, University of Minnesota Medical School, Minneapolis, MN, USA.
authors.forename: Jeremy
authors.initials: J
authors.lastname: Drees
authors.affiliation: Department of Medicine, Division of Hematology, Oncology, and Transplantation, University of Minnesota Medical School, Minneapolis, MN, USA.
authors.forename: Shaogeng
authors.initials: S
authors.lastname: Tang
authors.affiliation: Department of Medicine, Division of Hematology, Oncology, and Transplantation, University of Minnesota Medical School, Minneapolis, MN, USA.
authors.forename: Kerry
authors.initials: K
authors.lastname: Xiong
authors.affiliation: Department of Medicine, Division of Hematology, Oncology, and Transplantation, University of Minnesota Medical School, Minneapolis, MN, USA.
authors.forename: Hengbing
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Medicine, Division of Hematology, Oncology, and Transplantation, University of Minnesota Medical School, Minneapolis, MN, USA.
authors.forename: Jennifer E
authors.initials: JE
authors.lastname: Prigge
authors.affiliation: Department of Medicine, Division of Hematology, Oncology, and Transplantation, University of Minnesota Medical School, Minneapolis, MN, USA.
authors.forename: Alexander S
authors.initials: AS
authors.lastname: Dash
authors.affiliation: Department of Medicine, Division of Hematology, Oncology, and Transplantation, University of Minnesota Medical School, Minneapolis, MN, USA.
authors.forename: Andrea K
authors.initials: AK
authors.lastname: Kratzke
authors.affiliation: Department of Medicine, Division of Hematology, Oncology, and Transplantation, University of Minnesota Medical School, Minneapolis, MN, USA.
authors.forename: Emily
authors.initials: E
authors.lastname: Mesev
authors.affiliation: Department of Medicine, Division of Hematology, Oncology, and Transplantation, University of Minnesota Medical School, Minneapolis, MN, USA.
authors.forename: Ryan
authors.initials: R
authors.lastname: Etchison
authors.affiliation: Mayo Clinic, Department of Molecular Medicine, Rochester, MN, USA.
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Federspiel
authors.affiliation: Mayo Clinic, Department of Molecular Medicine, Rochester, MN, USA.
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Russell
authors.affiliation: Department of Medicine, Division of Hematology, Oncology, and Transplantation, University of Minnesota Medical School, Minneapolis, MN, USA.
authors.forename: Robert A
authors.initials: RA
authors.lastname: Kratzke
mesh_terms: D000818:Animals; D002289:Carcinoma, Non-Small-Cell Lung / Q000276:immunology* / Q000628:therapy* / Q000821:virology; D004195:Disease Models, Animal; D006801:Humans; D016899:Interferon-beta / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D008175:Lung Neoplasms / Q000276:immunology* / Q000628:therapy* / Q000821:virology; D051379:Mice; D008819:Mice, Nude; D050130:Oncolytic Virotherapy / Q000379:methods*; D050504:Oncolytic Viruses / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D014721:Vesicular stomatitis Indiana virus / Q000235:genetics / Q000276:immunology / Q000502:physiology*
chemical_list: D016899:Interferon-beta
keywords: NSCLC; Treg; VSV; interferon-β; oncolytic virus