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

Interferon-β (IFN-β) 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-β 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-β gene therapy, we hypothesized that combination of IFN-β gene therapy with immunotherapy might increase its effectiveness. In the present study, we tested whether combination therapy with IFN-β gene therapy and immunotherapy using tumor cell lysate-pulsed dendritic cells (DCs) would increase the efficacy of IFN-β gene therapy. In an experimental mouse intracranial glioma (GL261), which cannot be cured by either IFN-β gene therapy or DC immunotherapy alone, IFN-β 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.