RRC ID 43403
著者 Tatsuta K, Tanaka S, Tajiri T, Shibata S, Komaru A, Ueda Y, Inoue M, Hasegawa M, Suita S, Sueishi K, Taguchi T, Yonemitsu Y.
タイトル Complete elimination of established neuroblastoma by synergistic action of gamma-irradiation and DCs treated with rSeV expressing interferon-beta gene.
ジャーナル Gene Ther
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 gamma-irradiation pretreatment and recombinant Sendai virus (ts-rSeV/dF)-mediated murine interferon-beta (mIFN-beta) 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 gamma-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-beta through ts-rSeV/dF (ts-rSeV/dF-mIFNbeta-DCs) effectively reduced tumor size, and its combination with gamma-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-mIFNbeta-DCs with gamma-irradiation is a hopeful strategy for the treatment of intractable neuroblastomas, warranting further investigation in the clinical setting.
巻・号 16(2)
ページ 240-51
公開日 2009-2-1
DOI 10.1038/gt.2008.161
PII gt2008161
PMID 18987675
MeSH Animals Combined Modality Therapy Dendritic Cells / immunology Dendritic Cells / transplantation* Disease Models, Animal Female Gamma Rays / therapeutic use* Gene Transfer Techniques Genetic Therapy / methods* Genetic Vectors Interferon-beta / biosynthesis Interferon-beta / genetics* Mice Mice, Inbred A Neuroblastoma / immunology Neuroblastoma / pathology Neuroblastoma / radiotherapy Neuroblastoma / therapy* Sendai virus / genetics
引用数 10
WOS 分野 CHEMISTRY, ANALYTICAL BIOCHEMICAL RESEARCH METHODS
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リソース情報
ヒト・動物細胞 C-1300(RCB0283)