Effect of Bioreactor Process Control Parameters on Apoptosis and Monoclonal Antibody Production During the Protein-Free Fed-Batch Culture of a Murine Myeloma

Abstract

Apoptosis is now well known to occur in cell culture systems using commercially important cell lines, for example Chinese hamster ovary (CHO), SP2/0 and NSO myeloma cell lines. Apoptosis is undesirable in commercial production systems - culture productivity becomes diminished, the evolution of fragmented DNA may complicate downstream processing operations, and the proteases activated early in the apoptotic cascade may compromise the quality of any desired peptide or protein product. This study aimed to extend current knowledge by systematically investigating the effect of important process control parameters such as pH and temperature on the growth, death and productivity of a commercially important murine myeloma cell line producing a humanised monoclonal antibody during protein-free fed-batch culture.