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Productivity and quality of recombinant proteins produced by stable CHO cell clones can be predicted by transient expression in HEK cells

机译:稳定的CHO细胞克隆产生的重组蛋白的生产率和质量可以通过HEK细胞中的瞬时表达来预测

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摘要

Selection of lead candidates in drug discovery is a complex and time-consuming process. Here, we describe an approach that allows prediction of the productivity and quality of recombinant proteins by stable producer cell clones with the help of transient transfection studies. This is exemplified for three distinct bispecific T cell engager (BiTE~?) - a new class of single-chain antibody-based therapeutics showing very promising results in the treatment of cancer. BiTE~? titers of transiently transfected HEK cells showed a striking correlation with titers of selected stable CHO cell clones. Likewise, the percentage of the monomeric BiTE~? fraction in cell culture supernatants correlated well between transiently expressing HEK and stably expressing CHO cell clones. This validates the use of transient transfection studies for the selection of biopharmaceutical lead candidates with desired pharmaceutical properties.
机译:在药物发现中选择主要候选药物是一个复杂且耗时的过程。在这里,我们描述了一种方法,该方法可以通过瞬时转染研究,通过稳定的生产细胞克隆来预测重组蛋白的生产率和质量。这以三个不同的双特异性T细胞衔接子(BiTE-β)为例,这是一类新的基于单链抗体的疗法,在癌症治疗中显示出非常有希望的结果。 BiTE〜?瞬时转染的HEK细胞的滴度与选定的稳定CHO细胞克隆的滴度表现出惊人的相关性。同样,BiTE单体的百分比细胞培养上清液中的H2O3部分在瞬时表达的HEK和稳定表达的CHO细胞克隆之间有很好的相关性。这验证了瞬时转染研究在选择具有所需药物特性的生物药物潜在候选药物方面的应用。

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