Design of metamorphosis antibody molecule for cancer treatment and diagnosis

Research Project

Project/Area Number	18K19491
Research Category	Grant-in-Aid for Challenging Research (Exploratory)
Allocation Type	Multi-year Fund
Review Section	Medium-sized Section 50:Oncology and related fields
Research Institution	National Institutes of Biomedical Innovation, Health and Nutrition
Principal Investigator	Kamada Haruhiko 国立研究開発法人医薬基盤・健康・栄養研究所, 医薬基盤研究所創薬デザイン研究センター, プロジェクトリーダー (00324509)
Co-Investigator(Kenkyū-buntansha)	井上豪大阪大学, 薬学研究科, 教授 (20263204)
Project Period (FY)	2018-06-29 – 2020-03-31
Project Status	Completed (Fiscal Year 2019)
Budget Amount *help	¥6,240,000 (Direct Cost: ¥4,800,000、Indirect Cost: ¥1,440,000) Fiscal Year 2019: ¥3,120,000 (Direct Cost: ¥2,400,000、Indirect Cost: ¥720,000) Fiscal Year 2018: ¥3,120,000 (Direct Cost: ¥2,400,000、Indirect Cost: ¥720,000)
Keywords	抗体 / 二重特異性抗体 / 抗体分子 / 物性 / リンカー
Outline of Final Research Achievements	It is necessary to develop an antibody molecule having a new format in order to develop the antibody drug. In this study, we attempted to create a novel bispecific antibody that shows the alternative function. In thiis process, we found an interesting result that bispecific antibodies that recognize the same epitope have different characteristics and that named them metamorphosis antibody. In the in-vitro assay, it was found that the improvement of the thermal stability of BsAb itself is one of the factors leading to the improvement of the activity.
Academic Significance and Societal Importance of the Research Achievements	本研究では、抗体の構造学的変化から生物活性増強のメカニズムを解明することから、これまで活性が低いとされていた抗体の構造を改変し、優れた活性を持つ抗体へと最適化するための指針を解明できる可能性がある。さらに、抗原に結合した後の抗体のダイナミックな構造的変化が、その機能や生物活性に影響することが判明すれば、それらの情報を活用したがん治療法の開発や画期的診断薬の開発にも貢献できる可能性がある。