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CHO细胞表达重组抗人IL-17A/F单克隆抗体的培养基优化和质量评价

  • 吕美影 ,
  • 蒋俊凯 ,
  • 黄平周 ,
  • 张航烨 ,
  • 王迎港 ,
  • 梁育松 ,
  • 潘旭耀 ,
  • 邓钦培 ,
  • 冯春艳 ,
  • 许方岩 ,
  • 胡振湘
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  • 1珠海市丽珠单抗生物技术有限公司工艺开发部, 珠海 519045; 2珠海市丽珠单抗生物技术有限公司分析技术部, 珠海 519045; 3珠海市丽珠单抗生物技术有限公司, 珠海 519045

网络出版日期: 2025-08-16

Optimization and quality evaluation of the culture medium for the expression of a recombinant anti-human IL-17A/F monoclonal antibody in Chinese hamster ovary cells

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  • 1Process Development Department, Livzon Bio Inc., Zhuhai 519045, China; 2Analysis Technology Development Department, Livzon Bio Inc., Zhuhai 519045, China; 3Livzon Bio Inc., Zhuhai 519045, China

Online published: 2025-08-16

摘要

目的 优化表达抗人IL-17A/F单克隆抗体(单抗)的中国仓鼠卵巢(Chinese hamster ovary,CHO)细胞的培养基,筛选获得高表达且质量可比抗体的国产培养基。方法 用1株表达抗IL-17A/F单抗的CHO细胞,首先筛选出较优的基础培养基和补料培养基组合,并对该组合进行进一步补料策略优化和2 L生物反应器筛选,再经反应器工艺确认比较抗体表达量和产品质量。结果 基础培养基BM-01、补料培养基FM-01和FM-02组合为重组CHO细胞表达抗IL-17A/F单抗最优的培养基组合;其中补料培养基FM-01补料策略为培养第3/6/8/10/12天(3%~7%),补料培养基FM-01∶FM-02的补加体积比例为10∶1。在2 L生物反应器中最终抗体表达量超过6.5 g/L,为原工艺的2倍以上,且产品质量一致性好。结论 使用基础培养基BM-01、补料培养基FM-01和FM-02组合,实现了抗IL-17A/F单抗在CHO细胞中的高表达且质量可比,为国产培养基用于规模化生产抗IL-17A/F单抗奠定了基础。

本文引用格式

吕美影 , 蒋俊凯 , 黄平周 , 张航烨 , 王迎港 , 梁育松 , 潘旭耀 , 邓钦培 , 冯春艳 , 许方岩 , 胡振湘 . CHO细胞表达重组抗人IL-17A/F单克隆抗体的培养基优化和质量评价[J]. 国际生物制品学杂志, 2025 , 48(2) : 82 -90 . DOI: 10.3760/cma.j.cn311962-20240704-00045

Abstract

Objective To optimize the culture medium for Chinese hamster ovary (CHO) cells expressing anti-human IL-17A/F monoclonal antibody (anti-hIL-17A/F), and screen domestic culture media with high expression and comparable quality of antibody. Methods A CHO cell line expressing anti-hIL-17A/F was used to optimize the culture medium. The optimal basic medium and feed medium combination was selected, and the feed strategy optimization and 2 L bioreactor screening were carried out. Then the antibody expression and quality were measured in bioreactor final confirmation.Results The combination of basic medium BM-01, feed medium FM-01 and FM-02 was the optimal medium combination for the expression of anti-hIL-17A/F in recombinant CHO cells. Among them, the feed medium FM-01 was supplemented with a feed strategy of day3/6/8/10/12 (3%-7%), and the ratio of FM-01 to FM-02 was 10∶1. In 2 L bioreactor, the protein expression exceeded 6.5 g/L, more than twice of that of the original process, and the product quality was consistent.Conclusion High expression and comparable quality of anti-hIL-17A/F in CHO cells are achieved by using the combination of basic medium BM-01, feed medium FM-01 and FM-02, which lays a foundation for large-scale production of anti-hIL-17A/F using domestic culture media.
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