Increasing Cell Culture Yield with Targeted Metabolomics

Challenge: Highly Productive Cultures are Required to Meet the Demand

Monoclonal antibodies (mAbs) have become a valuable therapy for the treatment of a variety of diseases, including autoimmune disorders and cancer.¹ Chinese hamster ovary (CHO) cell lines are commonly used to produce mAbs due to their resilience to growth conditions and high protein synthesis capacity. Because mAb therapies usually require large doses over a long period, a large amount of mAbs must be manufactured to meet the demand. To meet the strong bioprocessing demand, it is important to develop a high-yield cell culture process.

Fed-batch cultures are widely utilized to produce therapeutic mAbs. The advantages of a fed-batch culture over batch culture are its higher product concentration, ease of operation, and faster development. However, fed-batch cell cultures require optimal cell culture medium and feed media to produce the highest yields of mAbs. Through metabolomics, scientists can uncover strategies for the design of culture media and feeds, leading to highly productive cultures.

Metabolon Insight: Advancing Cell Culture Productivity

Metabolon helped optimize a fed-batch culture media for mAb-producing CHO cells. Spent medium samples and cells were collected for metabolomics analysis using the Global Discovery Panel.

The Solution: Metabolomics Guides the Development of a Culture Medium

In this study, the goal was to develop a chemically defined basal medium and feed media for a fed-batch culture using a single CHO cell line. During the medium development, the spent media and cells were analyzed via targeted metabolomics to determine whether the concentrations of certain metabolites were limiting or excessive for cell growth and mAb yield.

Among the metabolites analyzed, choline was found to be one of the potential limiting nutrients in the fed-batch culture. The research group found that a choline limitation during the fed-batch culture caused a lower cell viability, a lower mAb titer, a higher mAb aggregate content, and a higher mannose-5 content.

Therefore, the group optimized the choline levels in the feeds. The optimized medium and feeds ultimately yielded a 6.4 g/L mAb titer, which was 12-fold higher than that of the initial batch culture using a commercially available, chemically defined CHO medium. They also showed that the basal and feed mediums worked well with several CHO cell lines, demonstrating that the developed basal medium and feed media are widely applicable.

The Outcome: Developing a High-Yield Cell Culture Process

Bioprocesses like the cell-based production of mAbs require optimal culture conditions to achieve the highest product quantity and quality. The quantification of a wide range of metabolites is a prerequisite to understanding and optimizing the underlying cell-based activities. In this study, Metabolon’s approach to bioprocess monitoring made it possible to determine the concentration of multiple metabolites in a simple and time-efficient manner. Targeted metabolomics allowed the development of an efficient fed-batch culture media for mAb-producing CHO cell lines.