Ultra-sensitive detection method of membrane antigens and its application to cancer companion diagnosis
Project/Area Number |
18H03936
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Research Category |
Grant-in-Aid for Scientific Research (A)
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Allocation Type | Single-year Grants |
Section | 一般 |
Review Section |
Medium-sized Section 37:Biomolecular chemistry and related fields
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Research Institution | Kyushu University |
Principal Investigator |
|
Co-Investigator(Kenkyū-buntansha) |
馬場 英司 九州大学, 医学研究院, 教授 (00315475)
浅井 大輔 昭和薬科大学, 薬学部, 准教授 (10423485)
森 健 九州大学, 工学研究院, 准教授 (70335785)
|
Project Period (FY) |
2018-04-01 – 2021-03-31
|
Project Status |
Completed (Fiscal Year 2020)
|
Budget Amount *help |
¥42,510,000 (Direct Cost: ¥32,700,000、Indirect Cost: ¥9,810,000)
Fiscal Year 2020: ¥11,570,000 (Direct Cost: ¥8,900,000、Indirect Cost: ¥2,670,000)
Fiscal Year 2019: ¥12,480,000 (Direct Cost: ¥9,600,000、Indirect Cost: ¥2,880,000)
Fiscal Year 2018: ¥18,460,000 (Direct Cost: ¥14,200,000、Indirect Cost: ¥4,260,000)
|
Keywords | 細胞膜抗原 / フローサイトメトリー / 蛍光分子プローブ / コンパニオン診断 / 酵素基質 / 分子プローブ / がん / がん診断 / 免疫組織化学 / 膜抗原 |
Outline of Final Research Achievements |
The project was performed to develop ultra-sensitive detection method of membrane antigens for cancer companion diagnostics. Firstly, we developed a new-type fluorescence probes that were converted from water soluble to hydrophobic with particular hydrolase labeled on antibody. These probes successfully detected low expression membrane antigens which can't detect with ordinary immuno-fluorescence. However, the accumulated fluorophore was gradually pumped out form the living cell and was re-taken up to other cells. This "color transfer" was serious issue for correct evaluation. After various investigations, we finally developed another strategy in which the hydrophilic probes acquired cell penetration ability and reactivity to cellular proteins with enzymatic reaction. This strategy solved the problem and successfully detected some low-expression antigens that are important to cancer companion diagnostics. Also, some new enzymes with no activities in human cells have been obtained.
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Academic Significance and Societal Importance of the Research Achievements |
最近、細胞(できれば生細胞)の機能を詳細に分別する必要性が高まっている。その最も直接的な方法は、フローサイトメトリーによる膜抗原の検出であるが、細胞の自家蛍光のため大半の重要な膜抗原は発現量が足りずに検出できない現状がある。今回開発した手法は、その問題を解決できるものであり、がんコンパニオン診断はもちろん、再生医療における幹細胞の純化など、これまで未達成の技術におけるブレイクスルーとなることが来た出来る。また、これらの目的にはヒト細胞で存在しない活性の酵素が必要であるが、これまでこのような観点からの酵素化学は存在しなかった。今回の研究ではその糸口がつかめたと言える
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Report
(4 results)
Research Products
(32 results)