Oncolytic influenza A virus expressing interleukin-15 decreases tumor growth in vivo

Surgery. 2017 Mar;161(3):735-746. doi: 10.1016/j.surg.2016.08.045. Epub 2016 Oct 21.

Abstract

Background: Interleukin-15 has become a promising molecule in the context of eliciting an effective, antitumor immune response because it is able to stimulate cells of the innate and adaptive immune system.

Methods: We generated an interleukin-15-expressing oncolytic influenza A virus for the treatment of an established murine tumor model.

Results: Our oncolytic influenza A virus produced large amounts of interleukin-15 and induced proliferation and activation of human T cells in vitro. Intraperitoneal administration increased the amount of mouse natural killer cells and effector memory T cells, as well as T cell reactivity in vivo. Moreover, intratumoral injection induced a profound decrease in growth of established tumors in mice and increased the amount of tumor-infiltrating T cells and natural killer cells.

Conclusion: We established a stable, IL-15-producing oncolytic influenza A virus with promising immunostimulatory and antitumor attributes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Culture Techniques
  • Cell Proliferation / drug effects
  • Female
  • Humans
  • Influenza A virus*
  • Interleukin-15 / physiology*
  • Killer Cells, Natural / drug effects
  • Melanoma, Experimental / pathology*
  • Melanoma, Experimental / therapy
  • Mice
  • Mice, Inbred C57BL
  • Oncolytic Virotherapy*
  • Oncolytic Viruses*
  • Skin Neoplasms / pathology*
  • Skin Neoplasms / therapy
  • T-Lymphocytes / drug effects

Substances

  • Interleukin-15