Elucidation and control of the aging in biopharmaceutical production cells

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K04794
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 27040:Biofunction and bioprocess engineering-related
• Research Institution: The University of Tokushima
• Principal Investigator: ONITSUKA Masayoshi 徳島大学, 大学院社会産業理工学研究部(生物資源産業学域), 講師 (80571174)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: 抗体医薬品 / CHO細胞 / 抗体品質制御 / バイオプロセス / N型糖鎖 / 連続培養

Outline of Final Research Achievements

In this study, recombinant CHO cells producing IgG1 antibodies were cultured continuously for an extended period of time to elucidate the relationship between aging-related enzymes and antibody quality. GLB1 and its related regulators were overexpressed in CHO cells and no changes in activity were observed. Continued research and verification of the relationship between senescence and antibody quality are necessary. On the other hand, in long-term continuous culture, the amount of terminal galactosylation of IgG1 antibody fluctuated wildly in response to changes in the culture conditions. Our analysis revealed the culture conditions under which the terminal galactosylation of the N-glycan structure was primarily enhanced. This result is expected to be useful for producing recombinant antibodies with high anti-tumor activity.

Free Research Field

細胞・バイオプロセス工学

Academic Significance and Societal Importance of the Research Achievements

抗体などのタンパク質医薬品は生産に用いる細胞や培養条件によって大きく変動するため、医薬品として最も重要視される「品質」のコントロールが難しい。近年、バイオ医薬品の品質を考えるうえで「クオリティ・バイ・デザイン（QbD）」という概念が着目されている。本研究は応用・実用を想定した基礎研究として、細胞培養条件と抗体医薬品の品質の関連性の解明に取り組んだ。連続培養を用いて培養条件を適切にコントロールする手法を考案し、重要品質特性の１つである糖鎖構造について品質向上の培養条件を同定した。これらの成果は「クオリティ・バイ・デザイン（QbD）」の実現に向けて大きな意義があると評価している。