| 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
|
| リソース情報 |
| ヒト・動物細胞 |
C-1300(RCB0283) |
