Antibodies targeting dynamic epitopes generated by posttranslational protein glycosylation

2022 Fiscal Year Final Research Report

• Project/Area Number: 19H00918
• Research Category: Grant-in-Aid for Scientific Research (A)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Medium-sized Section 37:Biomolecular chemistry and related fields
• Research Institution: Hokkaido University
• Principal Investigator: Nishimura Shin-Ichiro 北海道大学, 先端生命科学研究院, 教授 (00183898)
• Co-Investigator(Kenkyū-buntansha): 田中 良和 東北大学, 生命科学研究科, 教授 (20374225) ; 比能 洋 北海道大学, 先端生命科学研究院, 教授 (70333333) ; 尾瀬 農之 北海道大学, 先端生命科学研究院, 教授 (80380525)
• Project Period (FY): 2019-04-01 – 2023-03-31
• Keywords: Dynamic epitope theory / Glycopeptidic epitope / Epitope defined antibody / Anti-MUC1 mAb / がん治療用抗体 / X線結晶構造解析 / 機能改変抗体 / 二重特異性抗体

Outline of Final Research Achievements

In the present study, we succeeded in the development of novel antibodies and an innovative drug modality targeting various “dynamic epitopes” in the cell membrane-tethered MUC1 that accelerates cancer proliferation and metastasis. These antibody drug candidates uncovered that human pancreatic cancer cells express high level of MUC1 molecule bearing the dynamic epitope recognized by the antibody. Surprisingly, it was also demonstrated for the first time that exosomes derived from pancreatic cancer cells also display cargo MUC1 with the dynamic epitope on their membrane surface. Our findings will contribute to the acceleration of the development of anti-pancreatic cancer therapeutic antibody that has long remained unsuccessful.

Free Research Field

生物有機化学

Academic Significance and Societal Importance of the Research Achievements

本研究課題の大きな成果である「ダイナミックエピトープは未開拓の有力な標的分子の宝庫である」ということを示す多くの実験結果は、新たな視点と革新的な戦略に基づく「独創的な標的探索プラットホーム」の重要性と有効性を実証するものであり、今後このような戦略に基づく新たな診断システムや治療薬の開発が実現することで社会実装を見据えた応用研究への展開が大いに期待される。