| Project/Area Number |
10671605
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Otorhinolaryngology
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| Research Institution | Yokohama City University School of Medicine |
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Principal Investigator |
TSUKUDA Mamoru Professor, 医学部, 教授 (70142370)
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| Co-Investigator(Kenkyū-buntansha) |
MOCHIMATSU Izumi Associated professor, 医学部, 助教授 (10166332)
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| Project Period (FY) |
1998 – 1999
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| Project Status |
Completed (Fiscal Year 1999)
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| Budget Amount *help |
¥3,200,000 (Direct Cost: ¥3,200,000)
Fiscal Year 1999: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 1998: ¥1,900,000 (Direct Cost: ¥1,900,000)
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| Keywords | IL-2 / Gene therapy / Head and neck cancer / Basic studies |
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| Research Abstract |
Transduction of the human interleukin-2 (IL-2) gene into tumor cells was carried out in order to develop a new immunotherapy for advanced head and neck carcinomas with poor outcome. We transduced the IL-2 gene into KB cells, a head and neck squamous cell carcinoma cell line, using defective herpes simplex viral (HSV) amplicon vector as a gene transfer vehicle. A high level of IL-2 was secreted by IL-2 gene-transduced KB cells (KB/IL-2). The IL-2 producibility of irradiated KB/IL-2 cells was almost the same as that of non-irradiated cells. In the tumor establishment model in nude mice. IL-2 and interferon-γ (IFN-γ) at high concentrations were detected in the sera of mice transplanted with KB/IL-2 cells. The spleen cells of nude mice transplanted with KB/IL-2 cells exhibited high cytotoxic activity, compared to those from mice transplanted with KB cells and from untreated mice. Three of five mice transplanted with KB/IL-2 cells rejected tumors. In treatment of established tumors, therapeutic effects due to irradiated KB/IL-2 were dose-dependent. The suppressive effects on tumor growth were blocked by anti-asialo GM1, anti-human IL-2 and anti-IFN-γ antibodies. Immunohistochemical observation revealed the presence of asialo GM1ィイD1+ィエD1 cells among the KB/IL-2 cells in tumors transplanted into nude mice. Furthermore, the combination treatment of IL-2 gene therapy and exogenous murine IL-12 administration showed a synergistic anti-tumor effect. Based on these results, IL-2 gene therapy with or without IL-12 will be one of treatment strategies for advanced head and neck cancer cases with poor outcome.
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