Enhancement of Monoclonal Antibody Production under High Osmotic Pressure

Abstract

Based on the study respect to energy metabolism under high osmotic pressure and cell adaptation to the increase in osmotic pressure, a strategy of gradual increase in osmotic pressure was applied in monoclonal antibody (MAb) production. The specific production rate of MAb (qMAb) and MAb productivity at 388 mOsmol/kg were about 2 and 1.5 times higher, respectively, than those at the physiological osmotic pressure. The average specific rate of glucose consumption (vG) increased with osmotic pressure until 410 mOsmol/kg and then decreased. The specific consumption rate of glutamine (vGLN) increased slowly below 410 mOsmol/kg but rapidly above it. The yield of lactic acid from glucose (YL/G) increased above 410 mOsmol/kg and the yield of ammonia from glutamine increased monotonously with osmotic pressure which indicates a decreased energy yield from glucose and an increased energy yield from glutamine at osmolarity higher than 410 mOsmol/kg. Growth inhibition at 400 mOsmol/kg was greatly alleviated after incubated in 366 mOsmol/kg for 6 h. The intracellular osmoprotective amino acid contents were also reached highest at 6 h after incubation in 366 mOsmol/kg medium. With the strategy of gradual increase in osmotic pressure, MAb production was increased.