Physico-chemical and mathematical analyses of immune related signal induced by antibody aggregates
| Project/Area Number |
17H03975
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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 |
Physical pharmacy
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| Research Institution | Osaka University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
保仙 直毅 大阪大学, 医学系研究科, 教授 (10456923)
大戸 梅治 東京大学, 大学院薬学系研究科(薬学部), 准教授 (90451856)
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| Project Period (FY) |
2017-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥16,380,000 (Direct Cost: ¥12,600,000、Indirect Cost: ¥3,780,000)
Fiscal Year 2019: ¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000)
Fiscal Year 2018: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2017: ¥7,670,000 (Direct Cost: ¥5,900,000、Indirect Cost: ¥1,770,000)
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| Keywords | バイオ医薬 / 抗体医薬 / 安定性 / 凝集 / タンパク質 / 界面 / 免疫原性 / 分析 / バイオ医薬品 / 蛋白質 / 凝集体 / 質量分析 / 立体構造 / 抗体 / 免疫複合体 / TNF / 超遠心分析 / 沈降速度法 / 生体分子 / 薬学 / シグナル伝達 / バイオテクノロジー |
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| Outline of Final Research Achievements |
Based on this research, quantitative assessment of protein aggregates in biopharmaceuticals are established, and factors influencing protein aggregation as well as relation of immunological impact of protein aggregates were clarified. Specifically impact of protein-silicone oil drop released from syringe barrel protein complex on immune system is significant thus design of container is important. This study also indicate that interface stability of proteins are of importance to suppress protein aggregation, besides colloidal and conformational stabilities that have been pointed out as important factors for protein stability in solution. Based on this study,minimizing physical stress like vibration and impact should be a clue to stabilize therapeutic proteins in solution.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究は、近年、利用されているバイオ医薬品の安定性と安全性に関するものであるが、これまで不明点が多かったタンパク質凝集体と副作用の関係を実験的に示唆することができた社会的意義の大きい研究成果である。特に、製薬企業から医療現場で利用される実際の場面へとフィードバックが可能な知見が数多く含まれており、かつ、応急処置的な対応では無く、包括的かつ根本的に医薬品の安定性を高めることが可能となることから、科学的意義は当然ながら、産業的意義が大きいといえる。
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Report
(4 results)
Research Products
(62 results)
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[Journal Article] The Fab portion of immunoglobulin G contributes to its binding to Fcγ receptor III.2019
Author(s)
[Rina Yogo,Yuki Yamaguchi,Hiroki Watanabe,Hirokazu Yagi,Tadashi Satoh,Mahito Nakanishi,Masayoshi Onitsuka,Takeshi Omasa,Mari Shimada,Takahiro Maruno,Tetsuo Torisu,Shio Watanabe,Daisuke Higo,Takayuki Uchihashi,Saeko Yanaka,Susumu Uchiyama,Koichi Kato]
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Journal Title
Scientific Reports
Volume: 9
Issue: 1
Pages: 11957-11957
DOI
NAID
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Analytical ultracentrifugation with fluorescence detection 1 system reveals differences in complex formation between recombinant human TNFα and different biological TNFα antagonists in various environments.2017
Author(s)
Krayukhina, E., Noda, M., Ishii, K., Maruno, T., Wakabayashi, H., Tada, M., Suzuki, T., Ishii-Watabe, A., Kato, M., Uchiyama, S.
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Journal Title
mabs
Volume: 9
Issue: 4
Pages: 664-679
DOI
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
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