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首页> 外文会议>Cell culture engineering XV >IDENTIFICATION OF CELL CULTURE LEVERS TO LOWER TRISULFIDE MODIFICATIONS IN MONOCLONAL ANTIBODIES PRODUCED IN CHO CELL CULTURE
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IDENTIFICATION OF CELL CULTURE LEVERS TO LOWER TRISULFIDE MODIFICATIONS IN MONOCLONAL ANTIBODIES PRODUCED IN CHO CELL CULTURE

机译：CHO细胞培养产生的单克隆抗体中细胞培养物水平的低三硫修饰修饰

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Trisulfide bond formations are a commonly observed modification of monoclonal antibodies produced in cell culture processes. Protein trisulfide bonds are post-translational modifications in which an extra sulfur atom is bound between two cysteines involved in disulfide bonding. This modification has been detected in both recombinant and endogenous plasma-derived IgGs. Inconsistent levels of trisulfides were identified as a source of variability observed during the conjugation process for antibody-drug conjugates (ADCs). To understand the root cause for variable trisulfide levels observed during process development for different molecule projects, cell culture studies aimed at identifying process levers to minimize trisulfide formation were conducted. Several cell culture factors, including different media components, were identified and tested to lower product trisulfides and minimize the variability at time of harvest. An assessment of concerns about product trisulfide levels will be presented. Finally, identified levers and potential mechanism(s) involved in product trisulfide formation during cell culture will be discussed in this presentation.
机译：三硫键的形成是细胞培养过程中产生的单克隆抗体的常见修饰。蛋白三硫键是翻译后修饰，其中在参与二硫键的两个半胱氨酸之间结合了一个额外的硫原子。在重组和内源血浆衍生的IgG中都检测到了这种修饰。三硫化物水平不一致被确定为抗体-药物偶联物（ADC）偶联过程中观察到的变异性来源。为了了解在不同分子项目的工艺开发过程中观察到的三硫化物水平变化的根本原因，进行了旨在确定工艺杠杆以最小化三硫化物形成的细胞培养研究。鉴定并测试了几种细胞培养因子，包括不同的培养基成分，以降低三硫化物产物并最大程度地减少收获时的变异性。将提出对产品三硫化物含量的关注评估。最后，将在本演示文稿中讨论在细胞培养过程中与产物三硫化物形成有关的确定的杠杆和潜在机理。

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