Proteomics insight into the production of monoclonal antibody

Abstract The optimization of cell culture modes and basal media is very important to improve the production of therapeutic monoclonal antibodies (mAbs) by Chinese hamster ovary (CHO) cells, but the underlying cellular mechanism has not been well investigated. The objective of this study was to elucidate the interaction between the intracellular proteome and key process parameters by employing comparative proteomics. Three cell culture operations and four basal media were characterized in the production of anti-HER2 mAb using CHO DG44. The representative host cell proteins that demonstrated significant responses to various culture modes and media, including the enzymes involved in carbohydrate metabolism, transcription, translation, and post translational modification, were described. The fed-batch culture in a 2-L bioreactor produced mAb with a titer of 2411 mg/L using Dynamis medium. The purified mAb showed strong and specific targeting to HER2 + MDA-MB-361 cell and similar anti-cancer toxicity to the FDA approved Trastuzumab. Moreover, this proteomics study also indicated several key considerations for future rationally engineering a mAb production process, which could benefit biopharmaceutical manufacturing.