Complete elimination of established neuroblastoma by synergistic action of γ-irradiation and DCs treated with rSeV expressing interferon-β gene

K. Tatsuta, S. Tanaka, T. Tajiri, S. Shibata, A. Komaru, Y. Ueda, M. Inoue, M. Hasegawa, S. Suita, K. Sueishi, T. Taguchi, Y. Yonemitsu

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Abstract

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 7-9mm 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.

Original languageEnglish
Pages (from-to)240-251
Number of pages12
JournalGene Therapy
Volume16
Issue number2
DOIs
Publication statusPublished - 2009

All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • Molecular Biology
  • Genetics

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    Tatsuta, K., Tanaka, S., Tajiri, T., Shibata, S., Komaru, A., Ueda, Y., Inoue, M., Hasegawa, M., Suita, S., Sueishi, K., Taguchi, T., & Yonemitsu, Y. (2009). Complete elimination of established neuroblastoma by synergistic action of γ-irradiation and DCs treated with rSeV expressing interferon-β gene. Gene Therapy, 16(2), 240-251. https://doi.org/10.1038/gt.2008.161