Interferon-beta gene therapy inhibits tumor formation and causes regression of established tumors in immune-deficient mice

Proc Natl Acad Sci U S A. 1998 Nov 24;95(24):14411-6. doi: 10.1073/pnas.95.24.14411.


Despite the potential of type 1 interferons (IFNs) for the treatment of cancer, clinical experience with IFN protein therapy of solid tumors has been disappointing. IFN-beta has potent antiproliferative activity against most human tumor cells in vitro in addition to its known immunomodulatory activities. The antiproliferative effect, however, relies on IFN-beta concentrations that cannot be achieved by parenteral protein administration because of rapid protein clearance and systemic toxicities. We demonstrate here that ex vivo IFN-beta gene transduction by a replication-defective adenovirus in as few as 1% of implanted cells blocked tumor formation. Direct in vivo IFN-beta gene delivery into established tumors generated high local concentrations of IFN-beta, inhibited tumor growth, and in many cases caused complete tumor regression. Because the mice were immune-deficient, it is likely that the anti-tumor effect was primarily through direct inhibition of tumor cell proliferation and survival. Based on these studies, we argue that local IFN-beta gene therapy with replication-defective adenoviral vectors might be an effective treatment for some solid tumors.

MeSH terms

  • Adenoviridae
  • Animals
  • Breast Neoplasms / pathology
  • Breast Neoplasms / therapy*
  • Carcinoma, Hepatocellular
  • Cell Line
  • Colonic Neoplasms
  • Female
  • Genetic Therapy*
  • Genetic Vectors
  • Humans
  • Interferon-beta / biosynthesis
  • Interferon-beta / genetics*
  • Interferon-beta / physiology
  • Liver Neoplasms
  • Mice
  • Mice, Nude
  • Mice, SCID
  • Recombinant Proteins / biosynthesis
  • Time Factors
  • Transfection
  • Transplantation, Heterologous
  • Tumor Cells, Cultured
  • Uterine Cervical Neoplasms
  • beta-Galactosidase / biosynthesis
  • beta-Galactosidase / genetics


  • Recombinant Proteins
  • Interferon-beta
  • beta-Galactosidase