Cell Culture Engineering

Limiting lactate production in industrial CHO cell cultures

Biopharmaceuticals encompassing monoclonal antibodies (mAbs) and other protein therapeutics are among the most expensive of all drugs to manufacture. Mammalian cell culture processes are responsible for producing the vast majority of these compounds, which represent a total market of more than 100 billion dollars annually. The accelerating demand for mAb therapeutics has led to a critical need for enhanced productivity in mammalian cell culture bioprocesses. However, the push toward higher cell and product concentrations has been accompanied by the accumulation of inhibitory metabolites and increased apoptotic cell death, both of which limit product yields. Chief among these inhibitory metabolites is lactate; therefore, we are applying 13C-MFA to understand how lactate production is regulated in fed-batch cultures of industrial cell lines used to manufacture recombinant proteins. This understanding will be applied to design media formulations and genetic interventions that reduce lactate accumulation while improving cell viability and mAb productivity.

Funding support: NSF GOALI, Amgen
Graduate student: Neil Templeton
Key collaborators: Mike Betenbaugh (Johns Hopkins), Haimanti Dorai (Janssen Biotech), Pranhitha Reddy (Amgen)