通过在强化过程中延迟补充抗氧化剂来提高细胞特异性生产力
Suyang Wu1, Yen-An Lu1, Kyle Devenney1
1Biologics Process Research and Development, Merck & Co., Inc., Rahway, New Jersey, USA.
Biotechnology progress
|May 6, 2025
概括
在生长阶段后,补充中国仓鼠卵巢 (CHO) 细胞以迷酸 (RoA) 和乙乙 (RAc) 改善了抗体标位. 这种策略可以提高特定的生产力,而不妨碍细胞生长,优化生物过程的效率.
科学领域:
- 生物技术是生物技术.
- 细胞培养 细胞培养
- 生物制药制造业 生物制药制造业
背景情况:
- 抗氧化剂通常被添加到无血清介质中,以减少氧化应激和提高细胞培养生产率.
- 以前的研究表明抗氧化剂可以提高细胞生产力,但它们对CHO-GS细胞系生长和特定生产力的影响需要进一步研究.
研究的目的:
- 评估特定抗氧化剂 - - 罗斯马林酸 (RoA) 和乙乙 (RAc) - - 对表达双特异抗体的CHO-GS细胞系的特异性生产率的影响.
- 确定RoA和RAc的最佳补充策略,以提高抗体标位而不会对细胞生长产生负面影响.
主要方法:
- 食批量 (FB) 查发现RoA和RAc是有前途的抗氧化剂.
- 经过测试的RoA/RAc补充策略:在FB中的料中,在强化料批量 (iFB) 中,在连续制造 (CM) 的生产阶段.
- 对细胞生长,可活细胞密度,抗体标位和产品质量属性 (N-甘氨酸,碎片化,聚合) 的评估影响.
主要成果:
- 在指数增长阶段 (在料中,iFB或CM生产阶段) 后补充RoA/RAc有效增加了抗体标位.
- 这些策略提高了特定的生产力,但没有显著阻碍细胞生长或高峰可活细胞密度.
- 产品质量受到影响,N-甘氨酸曼诺的减少和碎片/聚合的增加,因工艺模式而异.
结论:
- 补充RoA/RAc后指数增长是一种可行的策略,可以改善CHO-GS细胞培养中的抗体标位.
- 抗氧化剂补充的时间和方式显著影响了标位增强和产品质量.
- 仔细评估抗氧化剂补充策略至关重要,考虑到被表达的特定细胞系和分子.
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