title: Culture temperature modulates monoclonal antibody charge variation distribution in Chinese hamster ovary cell cultures.
abstract: OBJECTIVE
  To investigate the effect of lowering culture temperature on monoclonal antibody charge variation distribution in Chinese hamster ovary cell cultures.
  
  
  RESULTS
  In both batch and fed-batch cultures, lowering the culture temperature decreased the antibody acidic variant levels. The acidic variant levels (defined as variants eluting earlier than the main peak of an antibody during HPLC) at 32 °C were about 10 % lower than those at 37 °C at the end of both batch and fed-batch cultures. Additionally, lowering the culture temperature increased the lysine variant level, which further increased basic variant level. The lysine variant levels at 32 °C were about 8 % (batch culture) and 3 % (fed-batch culture) higher than those at 37 °C at the end of cultures. Real-time PCR results suggests that the decrease in carboxypeptidase B transcription level might be partially responsible for the increased lysine variant level at sub-physiological temperatures.
  
  
  CONCLUSIONS
  Culture temperature exhibits noticeable impact on antibody charge variation distribution, especially the acidic variants and lysine variants.
authors.affiliation: The State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai, 200237, China. hongpingjiangnan@163.com.
authors.forename: Xintao
authors.initials: X
authors.lastname: Zhang
authors.affiliation: The State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai, 200237, China. scarun@163.com.
authors.forename: Ya-Ting
authors.initials: YT
authors.lastname: Sun
authors.affiliation: The State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai, 200237, China. thp_smile@hotmail.com.
authors.forename: Hongping
authors.initials: H
authors.lastname: Tang
authors.affiliation: The State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai, 200237, China. fanli@ecust.edu.cn.
authors.forename: Li
authors.initials: L
authors.lastname: Fan
authors.affiliation: The State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai, 200237, China. 020110101@mail.ecust.edu.cn.
authors.forename: Dongdong
authors.initials: D
authors.lastname: Hu
authors.affiliation: The State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai, 200237, China. jtliu0416@163.com.
authors.forename: Jintao
authors.initials: J
authors.lastname: Liu
authors.affiliation: The State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai, 200237, China. xupingliu@ecust.edu.cn.
authors.forename: Xuping
authors.initials: X
authors.lastname: Liu
authors.affiliation: The State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai, 200237, China. wstan@ecust.edu.cn.
authors.forename: Wen-Song
authors.initials: WS
authors.lastname: Tan
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000737:chemistry* / Q000302:isolation & purification / Q000378:metabolism; D061249:Batch Cell Culture Techniques / Q000379:methods*; D016466:CHO Cells; D049109:Cell Proliferation; D002852:Chromatography, Ion Exchange; D006224:Cricetinae; D003412:Cricetulus; D013696:Temperature
chemical_list: D000911:Antibodies, Monoclonal
keywords: Basic carboxypeptidase; Charge variation; Chinese hamster ovary cells; Culture temperature; Lysine variation; Monoclonal antibodies; Weak cation exchange chromatography