Innovative cancer-specific structural conversion design into high functional small bispecific antibodies
| Project/Area Number |
15H04306
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Tumor therapeutics
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| Research Institution | Tokyo University of Agriculture and Technology |
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Principal Investigator |
Asano Ryutaro 東京農工大学, 工学(系)研究科(研究院), 准教授 (80323103)
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| Co-Investigator(Kenkyū-buntansha) |
古本 祥三 東北大学, サイクロトロン・ラジオアイソトープセンター, 教授 (00375198)
真壁 幸樹 山形大学, 大学院理工学研究科, 准教授 (20508072)
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| Project Period (FY) |
2015-04-01 – 2018-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥16,770,000 (Direct Cost: ¥12,900,000、Indirect Cost: ¥3,870,000)
Fiscal Year 2017: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2016: ¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
Fiscal Year 2015: ¥6,240,000 (Direct Cost: ¥4,800,000、Indirect Cost: ¥1,440,000)
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| Keywords | 蛋白質 / がん / バイオテクノロジー / 癌 |
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| Outline of Final Research Achievements |
We tried to develop novel designs for bispecific antibodies which can be converted into functional format around cancer tissues. First, we integrated a recognition sequence of cancer specific protease into bispecific antibodies to convert into flexible format with high therapeutic effects around cancer. However, decreases in the activity were observed. Then, we integrated the same recognition sequence into a hinge region of Fc-fused bispecific antibody to convert into the small format with high tumor penetration ability from the format with long in vivo half-life. This design successfully produced functional small bispecific antibody by protease digestion.
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| Academic Significance and Societal Importance of the Research Achievements |
本提案では、がん組織に送達後にがん特異的に高機能型へと構造変換する新たな人工抗体のデザイン開発を進めた。一例として高分子量型の人工抗体の内部にがん特異的プロテアーゼの認識配列を挿入することで、がんに送達する前は長い体内半減期を有し、送達後には低分子型へと構造変換することでのがん組織への浸透性の向上を期待した分子の開発を行った。結果、プロテアーゼ消化により活性を維持したまま低分子化が認められた。今後の次世代型の抗体医薬開発の一助となることが期待される。
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Report
(4 results)
Research Products
(26 results)
