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 - Jan 1 2009

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Neuroblastoma
Interferons
Immunotherapy
Genes
Neoplasms
Sendai virus
Transgenes
Dendritic Cells
Immunity
Melanoma
Therapeutics

All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • Molecular Biology
  • Genetics

Cite this

Complete elimination of established neuroblastoma by synergistic action of γ-irradiation and DCs treated with rSeV expressing interferon-β gene. / Tatsuta, K.; Tanaka, S.; Tajiri, T.; Shibata, S.; Komaru, A.; Ueda, Y.; Inoue, M.; Hasegawa, M.; Suita, S.; Sueishi, K.; Taguchi, T.; Yonemitsu, Y.

In: Gene Therapy, Vol. 16, No. 2, 01.01.2009, p. 240-251.

Research output: Contribution to journalArticle

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, vol. 16, no. 2, pp. 240-251. https://doi.org/10.1038/gt.2008.161
Tatsuta, K. ; Tanaka, S. ; Tajiri, T. ; Shibata, S. ; Komaru, A. ; Ueda, Y. ; Inoue, M. ; Hasegawa, M. ; Suita, S. ; Sueishi, K. ; Taguchi, T. ; Yonemitsu, Y. / Complete elimination of established neuroblastoma by synergistic action of γ-irradiation and DCs treated with rSeV expressing interferon-β gene. In: Gene Therapy. 2009 ; Vol. 16, No. 2. pp. 240-251.
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