Efficient Production of Human Monoclonal Antibodies by an Improved Fructose-Based Human Cell Culture

摘要

Fructose-based culture is suitable for process control of human monoclonal antibody (MAb) production because of low lactate production or small pH change in culture medium, leading to cell and MAb stability. But not all human cell lines can proliferate in a fructose-based medium. We found that an active form of vitamin A, all-trans-retinoic acid (ATRA), improved proliferation of some human hybridomas in a fructose-based medium by stimulating fructose metabolism and boosted IgM and IgG production over the increase of proliferation.Although high cell density culture is efficient for human MAb production, its success is largely dependent of cell line and culture condition. We examined high cell density culture of human hybridomas in the improved fructose-based medium. As a result, it was possible to produce human MAb three times of high cell density culture in a conventional glucose-based medium. We reported here that the fructose-based medium supplemented with ATRA was useful for efficient production of human MAbs. This study might be applicable to other cell cultures susceptible to lactate or pH change as well as human cell cultures.