2023 Fiscal Year Final Research Report
Development of ultrasensitive detection method for call membrane antigen and its application to cancer companion diagnosis
| Project/Area Number |
21H04686
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| Research Category |
Grant-in-Aid for Scientific Research (A)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Review Section |
Medium-sized Section 34:Inorganic/coordination chemistry, analytical chemistry, and related fields
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| Research Institution | Kyushu University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
馬場 英司 九州大学, 医学研究院, 教授 (00315475)
森 健 九州大学, 工学研究院, 准教授 (70335785)
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| Project Period (FY) |
2021-04-05 – 2024-03-31
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| Keywords | がん診断 / フローサイトメトリー / 膜抗原 / 臨床診断 / コンパニオン診断 / 蛍光法 / 酵素増感法 / ELISA |
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| Outline of Final Research Achievements |
When we investigated the enzyme sensitization method that we had developed at the time of application, we found that the background increased due to the endogenous enzyme activity, which inhibited further sensitivity improvement, although we achieved improved sensitivity. Therefore, we came up with the idea of using enzymes that do not have endogenous activity in human cells, and through a search we succeeded in obtaining eight human orthogonal enzymes that are possessed by bacteria and plants and have no endogenous activity in mammals. When we created and investigated a coumarin-type substrate probe for one of these enzymes, we were able to significantly improve sensitivity by suppressing background. Furthermore, in order to achieve multiple colors, we devised a probe structure in which the quinone methide generating unit is independent from the fluorescent group, and succeeded in synthesizing it in the form of a coumarin.
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| Free Research Field |
分析化学
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| Academic Significance and Societal Importance of the Research Achievements |
がんコンパニオン診断は、個々のがんにおいて有効な制癌剤を選定するために必要不可欠であるが、現在、有効な手段がなく、薬剤の奏効率が低いことが大きな問題である。有効な診断法の開発を阻んでいる原因は、がんの機能(タイプ）を詳細に識別するために必要ながん細胞上の膜抗原の検出において、発現量が低くく有効な検出法が存在しないことである。本研究の成果は、酵素増感法とバックグラウンドを抑える内在活性のないヒト直交酵素の利用という新規な分析法の開発により、この問題を解決できたことであり、これにより原理的にはコンパニオン診断が可能になり、分析化学的にも社会的にも大きな意義がある。
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