Host cell impurities remaining after downstream purification of monoclonal antibodies has the potential to illicit adverse immune responses in patients and limit efficacy. Despite an extensive purification process, Chinese hamster ovary host cell proteins (HCP) have been found to appear with monoclonal antibodies (Mabs) after the purification process regardless of processing conditions. The presence of HCP over a long range of purification conditions suggests the possibility of product association in which HCP may directly interact or bind to Mabs. Due to the complex interaction landscape of many HCPs with product Mab, determination of particular processing conditions that reduce specific HCP-Mab interactions may lead to increased interactions of other HCPs, necessitating multi-dimensional approaches. Yeast surface display is a highly advantageous platform for library studies and fluorescent bar coding approaches which we use to simultaneously measure Mab association with many distinct HCP proteins. Starting with known CHO HCP such as lipoprotein lipase and Cathepsin D, we are developing a high-throughput yeast surface display assay to evaluate the HCP product association landscape over a range of solution conditions.

Multiplex characterization of Chinese hamster ovary host cell protein interactions with monoclonal antibodies by yeast surface display

255th National Meeting (2018)

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