Potent antitumor immunotherapy mediated by IL-18 gene transfection to PAM212 cells
| Project/Area Number |
14571918
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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 |
Surgical dentistry
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| Research Institution | Nihon University |
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Principal Investigator |
IWANARI Shinnkiti Nihon University, School of Dentistry, Department of Oral Maxillofacial Surgery, Research Associate, 歯学部, 助手 (30168588)
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| Co-Investigator(Kenkyū-buntansha) |
KOMIYAMA Kazuo Nihon University, School of Dentistry, Department of Pathology, Associate Professor, 歯学部, 助教授 (00120452)
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| Project Period (FY) |
2002 – 2003
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| Project Status |
Completed (Fiscal Year 2003)
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| Budget Amount *help |
¥4,000,000 (Direct Cost: ¥4,000,000)
Fiscal Year 2003: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 2002: ¥2,700,000 (Direct Cost: ¥2,700,000)
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| Keywords | IL-18 / PAM212 / Gene transfection / ICE / Antitumor effect / INF-g / oral / SCC / 癌遺伝子治療 / マウス / IFN-γ / 扁平上皮癌 / pam212 / 抗腫瘍効果 |
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| Research Abstract |
Increased number of oral cancer patient is currently consideration, which in Spite of developing operation technique and chemotherapy. Cancer gene therapy is one of new approaches against oral cancer. Initiation of the adaptive immune response is believed to be a result of local necrotic and apoptotic death of tissues and release of inflammatory cytokines by resident macrophages and recruited plymorphonuclear leukocytes. The cytokines released at the tumor site include IL-1, IL-6, IL-12 and IL-18, and other cytokines and chemokines. Dendritic cell recruitment and maturation is required for the induction of immune response. IL-18, INF-g-inducing factor, is a stimulatory factor in activation of Th1 cells that are major INF-g producing cells at tumor site. INF-g is up-regulate MHC class I and II expression on tumor cells. MHC class I is activated NK cells and macrophages and to help generate CD8+ cytotoxic T cells. In this study, IL-18 gene transfer to mouse squamous cell carcinoma cell (PAM212) was used to deliver cytokine to the tumor microenvironment. IL-18 single gene transfection of tumor cell ex vivo resulted in minimum effect of tumor regression, To generate active form of IL-18, it needs to IL-1b converting enzyme (ICE) to cleaved intercellular cysteine residue. Thus, dual transfection of IL-18 and ICE was performed in this study. Dual gene transfection study of tumor cell ex vivo resulted in 20% effect of tumor regression that was out of our respect. The reason of these results may be related to the transfection efficiency of the genes to PAM212 cells. We also injected ICE to IL-18/PAM212 bearing mouse, resulted in death of all animals because of toxicity. Therefore, future study required for develop the technique of transfection efficiency in the squamous cell carcinoma.
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Report
(3 results)
Research Products
(4 results)
