Heuristic Optimization of Antibody Production by Chinese Hamster Ovary Cells

• Published in: Biotechnology progress Vol. 21; no. 5; pp. 1537 - 1542
• Main Authors: Sandadi, Sandeepa, Ensari, Semsi, Kearns, Brian
• Format: Journal Article
• Language: English
• Published: USA American Chemical Society 01.09.2005; American Institute of Chemical Engineers
• Subjects: Algorithms; Animals; Antibodies, Monoclonal - biosynthesis; Biological and medical sciences; Biotechnology; Cell Culture Techniques - methods; CHO Cells - metabolism; Computer Simulation; Cricetinae; Cricetulus; Fundamental and applied biological sciences. Psychology; Glucose - metabolism; Glutamine - metabolism; Models, Biological; Protein Engineering - methods; Quality Control; Antibody; CHO cell line; Optimization; Production
• ISSN: 8756-7938; 1520-6033
• DOI: 10.1021/bp0501266

Large‐scale production of monoclonal antibodies necessitates the development of a commercially viable process using the appropriate bioreactors, culture medium, and optimal feeding strategies. In the development of feeding strategies for higher antibody titers it is critical to assess the effects of limiting substrates on cell culture longevity and antibody production. In this study, glucose and l‐glutamine were identified as limiting substrates and their effects on culture longevity and antibody production were evaluated in small‐scale experiments. The results suggested that an optimal feeding strategy should account for the osmolality profile of the culture. The heuristic approach taken to optimize the antibody production showed that the fed‐batch cultivation is superior to batch culture and maintaining low osmolality during growth phase increases cumulative viable cell density and thus leads to higher final antibody titer.