从单克隆抗体中减少高曼糖形式,通过使用重组 prokaryotic lectin 的亲属性染色学
Elizabeth Matthews1, Neha Tushar Dalvi1, Michael Butler2
1National Institute for Bioprocessing Research and Training, Foster Avenue, Mount Merrion, Blackrock, Co, Dublin A94 X099, Ireland.
Journal of biotechnology
|September 20, 2025
概括
一种新的莱克染色学方法有效地从单克隆抗体 (mAbs) 中去除高曼诺斯甘 (HM). 这种技术利用 prokaryotic 莱克来选择性地结合和减少 HM-glycans,改善生物制造的 mAb 质量.
科学领域:
- 生物制药制造业 生物制药制造业
- 葡萄糖生物学 葡萄糖生物学
- 蛋白质化学 蛋白质化学
背景情况:
- 单克隆抗体 (mAb) 甘氨酸形状是治疗疗效的关键质量属性.
- 在大规模的mAb生产过程中控制糖化是具有挑战性的.
- 高曼诺斯甘 (HM) 的增加可能会出乎意料地出现,影响mAb质量.
研究的目的:
- 开发和演示一种方法来从纯化的mAbs.中去除HM-甘氨酸.
- 评估基于 prokaryotic lectin 的染色学对 HM-glycan 减少的疗效.
- 为了评估该方法对整体mAb糖形状资料的影响.
主要方法:
- 开发一种使用RPL-Man2结合阿加罗斯珠的莱克染色法.
- 该方法应用于从培养在促进HM-甘氨酸形成的条件下培养的中国仓鼠卵巢 (CHO) 细胞中获得的mAbs.
- 使用UPLC与光检测和质谱学分析糖配置文件.
主要成果:
- 莱克染色学方法显著降低了纯化mAbs.中的HM-甘氨酸含量.
- 莱克的选择性结合并没有改变非HM糖形体的形状.
- 该方法在两个具有高HM-糖水平的不同抗体上进行了证明.
结论:
- 使用RPL-Man2的莱克染色学是一种有效的策略,用于减少mAbs.中的HM-甘氨酸.
- 这种方法显示了将其整合到大型生物制造工艺中的潜力.
- 选择性去除HM-甘氨酸可以帮助确保一致的mAb质量和治疗性能.
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