Impact of S-sulfocysteine on fragments and trisulfide bond linkages in monoclonal antibodies
Impact of S-sulfocysteine on fragments and trisulfide bond linkages in monoclonal antibodies
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DOI：
10.1080/19420862.2017.1333212
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发表时间：
2017-01-01
期刊：
影响因子：
5.3
通讯作者：
Zimmer, Aline
中科院分区：
文献类型：
--
作者：
Seibel, Ronja;Maier, Sandra;Zimmer, Aline
使用基于中国仓鼠卵巢细胞的哺乳动物系统生产的重组蛋白（如单克隆抗体）的质量取决于许多因素，包括细胞系、工艺和细胞培养基。由于这些因素，生成的产物是异质的，并且可能具有影响抗体稳定性、功能性以及在某些情况下影响患者安全性的化学诱导修饰或翻译后修饰。本研究表明，S-磺基半胱氨酸（一种半胱氨酸衍生物）可以增加用不同方法培养的不同细胞系中的抗体比生产率，同时最大限度地减少所产生mAb中的三硫键，主要是重链和轻链之间的三硫键。用S-磺基半胱氨酸补充细胞培养物进料也被证明可用于降低由单克隆抗体产生的抗体片段的百分比。总体而言，上游工艺中使用的这种新组分可降低产品异质性。
The quality of recombinant proteins such as monoclonal antibodies produced using Chinese hamster ovary cell-based mammalian systems is dependent on many factors, including cell line, process and cell culture media. Due to these factors, the generated product is heterogeneous and may have chemically-induced modifications or post-translational modifications that affect antibody stability, functionality and, in some cases, patient safety. This study demonstrates that S-sulfocysteine, a cysteine derivative, can increase the antibody specific productivity in different cell lines cultivated with different processes while minimizing trisulfide linkages in generated mAbs, mainly between heavy and light chain. The supplementation of a cell culture feed with S-sulfocysteine also proved to be useful to reduce the percentage of antibody fragments generated from the monoclonal antibody. Overall, this new component used in the upstream process allows a reduction of product heterogeneity.