VSV strains with defects in their ability to shutdown innate immunity are potent systemic anti-cancer agents

Cancer Cell. 2003 Oct;4(4):263-75. doi: 10.1016/s1535-6108(03)00241-1.


Ideally, an oncolytic virus will replicate preferentially in malignant cells, have the ability to treat disseminated metastases, and ultimately be cleared by the patient. Here we present evidence that the attenuated vesicular stomatitis strains, AV1 and AV2, embody all of these traits. We uncover the mechanism by which these mutants are selectively attenuated in interferon-responsive cells while remaining highly lytic in 80% of human tumor cell lines tested. AV1 and AV2 were tested in a xenograft model of human ovarian cancer and in an immune competent mouse model of metastatic colon cancer. While highly attenuated for growth in normal mice, both AV1 and AV2 effected complete and durable cures in the majority of treated animals when delivered systemically.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Active Transport, Cell Nucleus
  • Animals
  • Colonic Neoplasms / therapy
  • Colonic Neoplasms / virology
  • Female
  • Humans
  • Immunity, Innate / immunology
  • Immunity, Innate / physiology*
  • Interferon-beta / immunology
  • Interferon-beta / metabolism*
  • Lung Neoplasms / therapy
  • Lung Neoplasms / virology
  • Mice
  • Mice, Knockout
  • Models, Biological
  • Mutation
  • Neoplasms, Experimental / virology
  • Oligonucleotide Array Sequence Analysis
  • Ovarian Neoplasms / therapy
  • Ovarian Neoplasms / virology
  • Signal Transduction
  • Vesicular stomatitis Indiana virus / genetics
  • Vesicular stomatitis Indiana virus / metabolism*
  • Viral Matrix Proteins / metabolism
  • Virus Replication / genetics
  • Virus Replication / physiology


  • M protein, Vesicular stomatitis virus
  • Viral Matrix Proteins
  • Interferon-beta