Effect of polyamines on the N-glycosylation of antibody and its production.

2020 Fiscal Year Final Research Report

• Project/Area Number: 18K06652
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 47030:Pharmaceutical hygiene and biochemistry-related
• Research Institution: Tokyo University of Science
• Principal Investigator: HIGASHI KYOHEI 東京理科大学, 薬学部薬学科, 講師 (10463829)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: 抗体医薬 / ポリアミン / N-結合型糖鎖 / 小胞体ストレス

Outline of Final Research Achievements

Increased level of terminal galactosylation of N-glycan of antibody and decreased level of antibody production were found in polyamine-depleted cells. Thus, the genes whose expression level was enhanced by polyamines (polyamine modulon) were explored, however, it was found that polyamine depletion cause the ER stress because expression levels of BiP, carleticulin were increased in ployamine depleted cells. In addition, B4Gal-T1 level was also elevated in polyamine depleted cells. These results are consisted with the result of ER stress response caused by glucose starvation or tunicamycin treatment. Thus, these results suggest that polyamines influence the biosynthetic pathway of dolichol-linked oligosaccharide (DLO) on the endoplasmic reticulum. The experiments are in progress to identify the polyamine modulon in DLO sythetic pathway.

Free Research Field

分析化学、糖鎖生物学

Academic Significance and Societal Importance of the Research Achievements

糖鎖は細胞の環境や状態に応じてその構造が変化します。そのため、糖鎖を有する抗体医薬を細胞で生産する際には、その培養条件を非常に厳密にコントロールする必要があり、非常にコストがかかります。細胞増殖促進因子ポリアミンは細胞の状態に応じてその量が変化しますが、私達は今回、ポリアミンが抗体の糖鎖構造に影響を及ぼすことを明らかにしました。本研究で得られた成果は、安価で安定した抗体の生産技術の開発に資すると考えています。