Single-batch production of recombinant human polyclonal antibodies.
Single-batch production of recombinant human polyclonal antibodies.
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DOI：
10.1007/s12033-010-9270-9
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发表时间：
2010-07
影响因子：
2.6
通讯作者：
Tolstrup, Anne B.
中科院分区：
文献类型：
--
作者：
Nielsen, Lars S.;Baer, Alexandra;Muller, Christian;Gregersen, Kristian;Monster, Nina T.;Rasmussen, Soren K.;Weilguny, Dietmar;Tolstrup, Anne B.
关键词：
我们之前已经描述了一种利用定点整合产生的CHO细胞单批生产重组多克隆抗体(RpAb)的策略的开发和实施，即SympressTM I技术。SympressTM I技术在工业规模上实施，支持第二阶段临床开发计划。通过基于加入感兴趣基因的单一拷贝的定点整合来生产重组蛋白质，使SympressTM i技术最适合支持利基适应症。为了在保持低成本、高重复性的单批生产模式的同时提高效价，我们评估了许多不同的方法。最成功的结果是在一种名为ECHO的新生产细胞中随机集成，这是一种CHO DG44细胞衍生产品，旨在提高Symphogen的生产率。这种新的表达过程被称为SympressTM II技术。在这里，我们描述了证明原理的数据，证明了SympressTM II技术用于单批rpAb生产的可行性，使用了两个模型系统，每个模型系统由六个靶标特异性抗体组成。由ECHO细胞产生的rpAb的组成稳定性和批间重复性至少与以前使用定点整合技术观察到的一样好。此外，新工艺的效价有了显著的提高。
We have previously described the development and implementation of a strategy for production of recombinant polyclonal antibodies (rpAb) in single batches employing CHO cells generated by site-specific integration, the SympressTM I technology. The SympressTM I technology is implemented at industrial scale, supporting a phase II clinical development program. Production of recombinant proteins by site-specific integration, which is based on incorporation of a single copy of the gene of interest, makes the SympressTM I technology best suited to support niche indications. To improve titers while maintaining a cost-efficient, highly reproducible single-batch manufacturing mode, we have evaluated a number of different approaches. The most successful results were obtained using random integration in a new producer cell termed ECHO, a CHO DG44 cell derivative engineered for improved productivity at Symphogen. This new expression process is termed the SympressTM II technology. Here we describe proof-of-principle data demonstrating the feasibility of the SympressTM II technology for single-batch rpAb manufacturing using two model systems each composed of six target-specific antibodies. The compositional stability and the batch-to-batch reproducibility of rpAb produced by the ECHO cells were at least as good as observed previously using site-specific integration technology. Furthermore, the new process had a significant titer increase.
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影响因子：
2.9
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通讯作者：
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通讯作者：
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