Expressing human interleukin-15 from oncolytic vesicular stomatitis virus improves survival in a murine metastatic colon adenocarcinoma model through the enhancement of anti-tumor immunity

Cancer Gene Ther. 2012 Apr;19(4):238-46. doi: 10.1038/cgt.2011.81. Epub 2011 Dec 9.


In this study, we sought to enhance the potency of an oncolytic virus, vesicular stomatitis virus (VSV), by inserting a transgene encoding a highly secreted version of human interleukin-15 (IL-15). IL-15 has shown promise as an immunotherapeutic cytokine, as it is able to enhance both natural killer (NK) and T-cell responses, but it has not yet been tested as a therapeutic transgene in the context of viral oncolysis. The transgene was modified to ensure enhanced secretion of IL-15 from infected cells, leading to strong localized expression from infected CT-26 tumors in vivo. This localized expression in the tumor microenvironment led to a clear enhancement to anti-tumoral T-cell responses and enhanced survival, while additional IL-15 administration systemically failed to further enhance the therapy. Overall, the transient localized expression of IL-15 in the tumour by an oncolytic virus was able to induce stronger anti-tumoral immunity in a murine model of colon carcinoma.

MeSH terms

  • Adenocarcinoma / genetics
  • Adenocarcinoma / immunology
  • Adenocarcinoma / therapy*
  • Animals
  • Cell Line
  • Chlorocebus aethiops
  • Colonic Neoplasms / genetics
  • Colonic Neoplasms / immunology
  • Colonic Neoplasms / therapy*
  • Disease Models, Animal
  • Female
  • Gene Expression
  • Gene Order
  • Genetic Therapy
  • Genetic Vectors / administration & dosage
  • Genetic Vectors / genetics*
  • Humans
  • Interleukin-15 / genetics*
  • Killer Cells, Natural / immunology
  • Killer Cells, Natural / metabolism
  • Mice
  • Mice, Inbred BALB C
  • Neoplasm Metastasis
  • Oncolytic Virotherapy
  • Oncolytic Viruses / genetics*
  • Transduction, Genetic
  • Vesicular stomatitis Indiana virus / genetics*
  • Xenograft Model Antitumor Assays


  • Interleukin-15