2023 Fiscal Year Final Research Report
Fundamental study for the treatment of pancreatic cancer by a combination of chemotherapy and IL-18 function-blocking antibody
| Project/Area Number |
21K08753
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Review Section |
Basic Section 55020:Digestive surgery-related
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| Research Institution | Shimane University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
内田 有紀 島根大学, 医学部, 特別協力研究員 (60868719)
浦野 健 島根大学, 学術研究院医学・看護学系, 教授 (70293701)
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| Project Period (FY) |
2021-04-01 – 2024-03-31
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| Keywords | インターロイキン-18（IL-18） / 膵がん / 機能阻害抗体 / ５ーフルオロウラシル（5-FU） / 炎症性細胞死（パイロトーシス） |
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| Outline of Final Research Achievements |
We have generated and patented a monoclonal antibody that recognizes only "active IL-18" and has a strong inhibitory effect on the function of IL-18. Using this antibody, we investigated the mechanism of human IL-18 activation in pancreatic cancer cell lines and found that both the hypotrophic microenvironment of pancreatic cancer cells and treatment with the anti-tumor drug 5-FU may induce inflammation through IL-18 activation via pyroptosis, which is inflammatory cell death. The combination of anti-tumor drugs and the antibody that inhibits IL-18 function could lead to a new therapeutic approach for pancreatic cancer.
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| Free Research Field |
消化器外科
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| Academic Significance and Societal Importance of the Research Achievements |
「活性型 IL-18」のみを認識し、強い機能阻害効果を持つモノクローナル抗体を作製・報告し特許を取得した。この抗体を作製・保有していたことで、膵がんや大腸がんなどでも使用される抗腫瘍薬 5-FU が膵がん細胞の低栄養微小環境と相まって活性型 IL-18 を誘導させることを初めて確認できた。活性型 IL-18 を対象にした新規治療法や診断応用の確立に向けた研究を独自に進められる。
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