Vaccination with tumor cell lysate-pulsed dendritic cells augments the effect of IFN-beta gene therapy for malignant glioma in an experimental mouse intracranial glioma

Int J Cancer. 2004 Sep 20;111(5):777-82. doi: 10.1002/ijc.20331.

Abstract

Interferon-beta (IFN-beta) has been used as an antitumor drug against human glioma, melanoma and medulloblastoma since the 1980s. Recently, we developed a new gene therapy using the IFN-beta gene against malignant gliomas and then began clinical trials in 2000. Since stimulation of immune system was one mechanism of antitumor effect induced by IFN-beta gene therapy, we hypothesized that combination of IFN-beta gene therapy with immunotherapy might increase its effectiveness. In the present study, we tested whether combination therapy with IFN-beta gene therapy and immunotherapy using tumor cell lysate-pulsed dendritic cells (DCs) would increase the efficacy of IFN-beta gene therapy. In an experimental mouse intracranial glioma (GL261), which cannot be cured by either IFN-beta gene therapy or DC immunotherapy alone, IFN-beta gene therapy following DC immunotherapy resulted in a significant prolongation in survival of the mice. Moreover, when this combination was performed twice, 50% of treated mice survived longer than 100 days. Considering these results, this combination therapy may be one promising candidate for glioma therapy in the near future.

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology*
  • Brain Neoplasms / genetics*
  • Brain Neoplasms / therapy*
  • Brain Neoplasms / veterinary
  • Cancer Vaccines*
  • Combined Modality Therapy
  • Dendritic Cells / immunology*
  • Female
  • Genetic Therapy*
  • Glioma / genetics*
  • Glioma / therapy*
  • Glioma / veterinary
  • Immunotherapy
  • Interferon-beta / genetics*
  • Interferon-beta / pharmacology*
  • Lipids
  • Mice
  • Mice, Inbred C57BL
  • Neoplasms, Experimental
  • Plasmids
  • Tumor Cells, Cultured

Substances

  • Antineoplastic Agents
  • Cancer Vaccines
  • Lipids
  • Interferon-beta