Convenient isolation and generation of fully human antibodies

• Project/Area Number: 15K16328
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Biomedical engineering/Biomaterial science and engineering
• Research Institution: National Institute of Infectious Diseases
• Principal Investigator: Ainai Akira 国立感染症研究所, 感染病理部, 主任研究官 (10572133)
• Project Period (FY): 2015-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000); Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2015: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
• Keywords: ヒト抗体 / B細胞 / 抗体

Outline of Final Research Achievements

The aim of this study was easy and simplified generation of fully human antibodies for therapeutic purpose against infectious diseases. In this study, “culture condition for transient propagation of human B cells” and “selection method of human memory B cells bearing antigen-specific surface antibody” were investigated. Cultivation of B cells in the presence of the combination of five stimulations (that is, ODN2006, BAFF, IL-15, soluble CD40-ligand and IL-6) was the most effective for transient propagation of them. The panning against antigen was chosen for the selection of human memory B cells, however, B cells bearing non-specific antibody against antigen were not completely excluded.

Academic Significance and Societal Importance of the Research Achievements

感染症の治療あるいは予防に応用可能な抗体医薬の開発は遅れている。現在主に利用されている抗体医薬はIgG抗体に限定されているが、IgA抗体による抗体医薬が開発できれば、粘膜経由で感染するウイルスや細菌に対して有益な治療・予防の手段になり得ると期待できる。有用なヒト抗体の選択法に関してはいくつかの手法が考案されているが、それぞれ利点・欠点がある。より簡便かつ効率のより有用なヒト抗体の選択法が確立できれば、抗体医薬開発に大きく貢献できると思われる。