Proteomic and metabolomic characterization of CHO DP-12 cell lines with different high passage histories

Abstract

Background For industrial pharmaceutical protein production fast growing, high producing and robust cell lines are required. To select more pH shift permissive and fast growing sub-populations, the CHO DP-12 (ATCC clone #1934) cell line, an anti-IL8 antibody producing CHO K1 (DHFR) clone, was continuously subcultured at high viability (>90 %) for more than four hundred days in shaking flasks using a chemically defined medium. During this long-term cultivation there was a repeated shift in pH and most robust and fast growing cells became accumulated [1]. Cell samples were cryopreserved at four different time points, after 21, 95, 165 and 420 days (in the following named sub-populations (SP)). The effects of long-term passaging before cryopreservation correlating with an increase in specific growth rate as well as changes in product formation and metabolism were examined in parallel bench-top bioreactor cultivation of SP21, SP95, SP165 and SP420 sub-populations. During exponential growth phase samples were taken for the analyses of differences in intracellular metabolites and protein expression (Please consider article “Growth characterization of CHO DP-12 cell lines with different high-passage histories” by Heinrich et al. in this issue for a detailed discussion of long-term cultivation, changes in specific growth rate, product formation and metabolic shifts).