Expression of IFN-beta enhances both efficacy and safety of oncolytic vesicular stomatitis virus for therapy of mesothelioma

Cancer Res. 2009 Oct 1;69(19):7713-20. doi: 10.1158/0008-5472.CAN-09-1013. Epub 2009 Sep 22.


Our preclinical and clinical trials using a replication-defective adenoviral vector expressing IFN-beta have shown promising results for the treatment of malignant mesothelioma. Based on the hypotheses that a replication-competent vesicular stomatitis virus (VSV) oncolytic vector would transduce more tumor cells in vivo, that coexpression of the immunostimulatory IFN-beta gene would enhance the immune-based effector mechanisms associated both with regression of mesotheliomas and with VSV-mediated virotherapy, and that virus-derived IFN-beta would add further safety to the VSV platform, we tested the use of IFN-beta as a therapeutic transgene expressed from VSV as a novel treatment for mesothelioma. VSV-IFN-beta showed significant therapy against AB12 murine mesotheliomas in the context of both local and locoregional viral delivery. Biologically active IFN-beta expressed from VSV added significantly to therapy compared with VSV alone, dependent in part on host CD8+ T-cell responses. Immune monitoring suggested that these antitumor T-cell responses may be due to a generalized T-cell activation rather than the priming of tumor antigen-specific T-cell responses. Finally, IFN-beta also added considerable extra safety to the virus by providing protection from off-target viral replication in nontumor tissues and protected severe combined immunodeficient mice from developing lethal neurotoxicity. The enhanced therapeutic index provided by the addition of IFN-beta to VSV therefore provides a powerful justification for the development of this virus for future clinical trials.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Epitopes, T-Lymphocyte / immunology
  • Genetic Therapy / methods
  • Humans
  • Interferon-beta / biosynthesis
  • Interferon-beta / genetics*
  • Interferon-beta / immunology
  • Mesothelioma / genetics
  • Mesothelioma / immunology
  • Mesothelioma / therapy*
  • Mesothelioma / virology
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Mice, SCID
  • Nervous System Diseases / virology
  • Oncolytic Virotherapy / methods*
  • T-Lymphocytes / immunology
  • Vesiculovirus / genetics*


  • Epitopes, T-Lymphocyte
  • Interferon-beta