Complete elimination of established neuroblastoma by synergistic action of |[gamma]|-irradiation and DCs treated with rSeV expressing interferon-|[beta]| gene

Dendritic cell (DC)-based immunotherapy has been investigated as a new therapeutic approach to intractable neuroblastomas; however, only limited clinical effect has been reported. To overcome the relatively low sensitivity of neuroblastomas against immunotherapy, we undertook a preclinical efficacy study to examine murine models to assess the combined effects of γ-irradiation pretreatment and recombinant Sendai virus (ts-rSeV/dF)-mediated murine interferon-β (mIFN-β) gene transfer to DCs using established c1300 neuroblastomas. Similar to intractable neuroblastomas in the clinic, established c1300 tumors were highly resistant to monotherapy with either γ-irradiation or DCs activated by ts-rSeV/dF without transgene (ts-rSeV/dF-null) that has been shown to be effective against other murine tumors, including B16F10 melanoma. In contrast, immunotherapy using DCs expressing mIFN-β through ts-rSeV/dF (ts-rSeV/dF-mIFNβ-DCs) effectively reduced tumor size, and its combination with γ-irradiation pretreatment dramatically enhanced its antitumor effect, resulting frequently in the complete elimination of established c1300 tumors 7–9 mm in diameter, in a high survival rate among mice, and in the development of protective immunity in the mice against rechallenge by the tumor cells. These results indicate that the combination of ts-rSeV/dF-mIFNβ-DCs with γ-irradiation is a hopeful strategy for the treatment of intractable neuroblastomas, warranting further investigation in the clinical setting.