| Project/Area Number |
18K19406
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| Research Category |
Grant-in-Aid for Challenging Research (Exploratory)
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| Allocation Type | Multi-year Fund |
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| Review Section |
Medium-sized Section 47:Pharmaceutical sciences and related fields
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| Research Institution | Kyushu University |
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Principal Investigator |
Tadashi Ueda 九州大学, 薬学研究院, 教授 (90184928)
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| Co-Investigator(Kenkyū-buntansha) |
宗 孝紀 富山大学, 学術研究部薬学・和漢系, 教授 (60294964)
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| Project Period (FY) |
2018-06-29 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥6,240,000 (Direct Cost: ¥4,800,000、Indirect Cost: ¥1,440,000)
Fiscal Year 2019: ¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
Fiscal Year 2018: ¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000)
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| Keywords | ADAs / 免疫寛容 / 蛋白質デリバリー法 / リゾチーム / βラクトグロブリン / Fab / CH2ドメイン |
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| Outline of Final Research Achievements |
The goal of this project was to examine whether induction of the immune tolerance obtained in my laboratory using polymeric hen egg-while lysozyme (HEL) could be applicable to the depression of Anti-Drug Antibodies or not.One week after the preinjection of polymeric HEL, polymeric beta-lactalbumin and polymeric humanized Fab dissolved in phosphate buffer-saline in mice, respectively, an emulsion of each protein monomer (HEL、beta-lactalbumin and humanized Fab) dissolved in phosphate buffer-saline with adjuvant was injected in mice. The amounts of specific antibody against each protein monomer were evaluated every week. As a result, the immune tolerance against polymeric HEL was observed. However, the immune tolerance against polymeric beta-lactalbumin and polymeric humanized Fab were not observed.
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| Academic Significance and Societal Importance of the Research Achievements |
ニワトリリゾチームの多量体が免疫寛容（マウスにとって異物と認識されない）を引き起こすが、βラクトグロブリンやヒト型Fab（抗体の一部）の多量体では引き起こさないという結果を得ることができた。この結果から、マウス体内で塩基性蛋白質であるニワトリリゾチーム多量体が正電荷のクラスターを形成し、マウス体内で表面に負電荷を持つ細胞に効率的にデリバリーされ、免疫寛容誘導が起こった可能性がある。さらなる検証が必要であるが、この仮説が実証できれば、細胞へ人為的に蛋白質をデリバリーする方法の開発ができるのではないか。ついては、ヒトの免疫応答を調節可能な生体材料の創製につながる。
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