{
  "abstract": "Background Vesicular stomatitis virus (VSV) pseudotyped with the glycoprotein (GP) of the lymphocytic choriomeningitis virus (VSV-GP) represents a potent oncolytic virus (OV). Oncolytic virotherapy is an emerging anticancer approach that uses viruses to eliminate cancer cells by direct cell lysis and induction of an antitumor immune response. Immunomodulatory cargos expressed by OVs hold the potential to further enhance this antitumor immune response.Methods To evaluate interleukin-12 (IL-12) as an immunomodulatory cargo encoded by VSV-GP, we used a subcutaneous tumor model by mixing type I interferon (IFN) competent murine lung epithelial cells (TC-1), which are largely resistant to VSV-GP in vivo, with VSV-GP permissive IFN-α receptor knockout TC-1 cells (TC-1 ifnar1 −/ −).Results This mixed model supports prolonged viral replication and subsequent IL-12 production. Oncolytic virotherapy with VSV-GP and VSV-GP-IL12 of parental TC-1 tumors did not lead to tumor control, whereas virus treatment in the TC-1/TC-1 ifnar1 −/− mixed tumors showed prolonged survival. Furthermore, VSV-GP-IL12 was even more effective than VSV-GP treatment. Analysis of CD8+ T cell responses revealed phenotypic differences of activated CD8+ T cells between VSV-GP and VSV-GP-IL-12 treatment, whereby VSV-GP-IL12-induced CD8+T cells displayed a phenotype described for long-lived effector cells (LLEC). Depletion experiments indicated that CD8+ T cells, and not NK cells, were responsible for the improved efficacy observed with VSV-GP-IL12 treatment.Conclusions Taken together, we have demonstrated that oncolytic virotherapy using VSV-GP encoding IL-12 induces CD8+ T cell responses characterized by an LLEC phenotype, a cell population that is likely a crucial component of antitumor immunity.",
  "authors": [
    {
      "affiliations": [
        "Institute of Virology, Medical University of Innsbruck, Innsbruck, Tirol, Austria"
      ],
      "name": "Jasmin Hatami"
    },
    {
      "affiliations": [
        "ViraTherapeutics GmbH, Rum, Tyrol, Austria"
      ],
      "name": "Krishna Das"
    },
    {
      "affiliations": [
        "Institute of Virology, Medical University of Innsbruck, Innsbruck, Tirol, Austria"
      ],
      "name": "Leonie Wolf"
    },
    {
      "affiliations": [
        "Christian Doppler Laboratory for Viral Immunotherapy, Institute of Virology, Medical University of Innsbruck, Innsbruck, Tirol, Austria",
        "Department of Internal Medicine V, Tyrolean Cancer Research Center, Medical University of Innsbruck, Innsbruck, Tyrol, Austria"
      ],
      "name": "Andreas Aufschnaiter"
    },
    {
      "affiliations": [
        "Institute of Virology, Medical University of Innsbruck, Innsbruck, Tirol, Austria"
      ],
      "name": "Janine Kimpel"
    },
    {
      "affiliations": [
        "ViraTherapeutics GmbH, Rum, Tyrol, Austria"
      ],
      "name": "Tobias Nolden"
    },
    {
      "affiliations": [
        "Christian Doppler Laboratory for Viral Immunotherapy, Institute of Virology, Medical University of Innsbruck, Innsbruck, Tirol, Austria"
      ],
      "name": "Liesa-Marie Schreiber"
    },
    {
      "affiliations": [
        "Institute of Virology, Medical University of Innsbruck, Innsbruck, Tirol, Austria"
      ],
      "name": "Brigitte Müllauer"
    },
    {
      "affiliations": [
        "ViraTherapeutics GmbH, Rum, Tyrol, Austria"
      ],
      "name": "Elke Podgorschek"
    },
    {
      "affiliations": [
        "ViraTherapeutics GmbH, Rum, Tyrol, Austria"
      ],
      "name": "Theresa Schwaiger"
    },
    {
      "affiliations": [
        "ViraTherapeutics GmbH, Rum, Tyrol, Austria"
      ],
      "name": "Bart Spiesschaert"
    },
    {
      "affiliations": [
        "Christian Doppler Laboratory for Viral Immunotherapy, Institute of Virology, Medical University of Innsbruck, Innsbruck, Tirol, Austria",
        "Department of Internal Medicine V, Tyrolean Cancer Research Center, Medical University of Innsbruck, Innsbruck, Tyrol, Austria"
      ],
      "name": "Guido Wollmann"
    },
    {
      "affiliations": [
        "ViraTherapeutics GmbH, Rum, Tyrol, Austria"
      ],
      "name": "Knut Elbers"
    },
    {
      "affiliations": [
        "Institute of Virology, Medical University of Innsbruck, Innsbruck, Tirol, Austria"
      ],
      "name": "Dorothee von Laer"
    },
    {
      "affiliations": [
        "Institute of Virology, Medical University of Innsbruck, Innsbruck, Tirol, Austria"
      ],
      "name": "Zoltán Bánki"
    }
  ],
  "title": "Interleukin-12 encoded by the oncolytic virus VSV-GP enhances therapeutic antitumor efficacy by inducing CD8+ T-cell responses with a long-lived effector cell phenotype",
  "uid": "70191c47-7280-5074-b6d2-220019cd44a5"
}