Qin Yongjun, Ma Rongmei, Li Yang, Li Yifeng, Chen Gong, Zhou Weichang
Technology and Process Development (TPD), WuXi Biologics, 288 Fute Zhong Road, Waigaoqiao Free Trade Zone, Shanghai 200131, China.
Biologics Development, WuXi Biologics, 288 Fute Zhong Road, Waigaoqiao Free Trade Zone, Shanghai 200131, China.
Antib Ther. 2022 May 3;5(2):111-120. doi: 10.1093/abt/tbac009. eCollection 2022 Apr.
Aggregation, fragmentation, and low yield are issues frequently found during the cell culture process of bispecific antibodies (bsAbs), whose inherent complexity likely plays a role in causing these issues.
In this study, we made a head-to-head comparison between fed-batch cell culture and intensified perfusion cell culture with a symmetric bsAb case.
In comparison with the fed-batch culture, a 6.6-fold improvement in integrated viable cell density and a 10.9-fold improvement in volumetric productivity were achieved with the intensified perfusion mode. In addition, a significant decrease in aggregation and fragmentation was observed with the intensified perfusion cell culture. Furthermore, product homogeneity was improved, which was reflected by the increased percentage of capillary isoelectric focusing main group. The quality improvement with intensified perfusion cell culture can be attributed to the shortened product retention in the bioreactor.
These findings suggest that intensified perfusion cell culture could be a better choice than traditional fed-batch especially for complex molecules like bsAbs. As this is a single case report, future studies on other cases are needed to further confirm the general applicability of this strategy.
双特异性抗体（bsAbs）细胞培养过程中经常出现聚集、片段化和低产量问题，其内在复杂性可能是导致这些问题的原因之一。
在本研究中，我们对补料分批细胞培养和强化灌注细胞培养在一种对称双特异性抗体情况下进行了直接比较。
与补料分批培养相比，强化灌注模式下的综合活细胞密度提高了6.6倍，体积生产力提高了10.9倍。此外，强化灌注细胞培养中聚集和片段化显著减少。此外，产品均一性得到改善，这通过毛细管等电聚焦主峰百分比的增加得以体现。强化灌注细胞培养带来的质量提升可归因于生物反应器中产品保留时间的缩短。
这些发现表明，强化灌注细胞培养可能是比传统补料分批培养更好的选择，特别是对于像双特异性抗体这样的复杂分子。由于这是一个单病例报告，需要对其他病例进行进一步研究以进一步确认该策略的普遍适用性。
