Efficient Development of a Stable Cell Pool for Antibody Production Using a Single Plasmid.

Therapeutic antibodies are the fastest growing group of biopharmaceuticals. Evaluation of drug candidates requires a sufficient amount of antibodies. Production of antibodies with stable cell pools is an efficient strategy to produce grams of proteins for drug candidate selection. Many methods have been described for developing stable cell pools for antibody expression. However, most of the reported methods are laborious due to the low frequency of high producers. In this study, we determined optimal vectors and screening parameters to develop a strategy for efficient construction of stable antibody expressing cell pools. The cell pool constructed using the optimized strategy consistently yielded a higher expression titer, up to 10-fold improvement. Further, this method resulted in a higher ratio of the cell pools with the main product peak above 95% as assessed by size-exclusion chromatography. High producers could be obtained by means of screening five 96-well plates. This strategy will greatly reduce clone-screening size during Clinical Lead Selection. This study provides a platform with efficient design of plasmids and screening strategies for significant cost and labour savings in high expression of two-subunit proteins such as antibodies.