Fundamental study on depression of Anti-Drug Antibodies by use of immune tolerance

2019 Fiscal Year Final Research Report

• Project/Area Number: 18K19406
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Review Section: Medium-sized Section 47:Pharmaceutical sciences and related fields
• Research Institution: Kyushu University
• Principal Investigator: Tadashi Ueda 九州大学, 薬学研究院, 教授 (90184928)
• Co-Investigator(Kenkyū-buntansha): 宗 孝紀 富山大学, 学術研究部薬学・和漢系, 教授 (60294964)
• Project Period (FY): 2018-06-29 – 2020-03-31
• Keywords: ADAs / 免疫寛容 / 蛋白質デリバリー法

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.

Free Research Field

生物系薬学

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。