不同细胞培养基对抗破伤风毒素人源单抗关键质量属性的影响  

Effects of different cell culture media on critical quality attributes of human monoclonal antibody against tetanus toxin

作　　者：王建锋 汪艳艳 郭岚 叶星 南建军 安晨 宋兰兰 陈继军 毛晓燕 WANG Jian-feng;WANG Yan-yan;GUO Lan;YE Xing;NAN Jian-jun;AN Chen;SONG Lan-lan;CHEN Ji-jun;MAO Xiao-yan(Lanzhou Institute of Biological Products,Co.,Ltd,Engineering Research Center of Macromolecules Biological Drugs of Gansu Province,Vaccinal Engineering Technology Research Center of Gansu Province,Lanzhou 730046,Gansu Province,China)

机构地区：[1]兰州生物制品研究所有限责任公司,甘肃省大分子蛋白生物药工程研究中心,甘肃省疫苗工程技术研究中心,甘肃兰州730046

出　　处：《中国生物制品学杂志》2021年第11期1300-1306,共7页Chinese Journal of Biologicals

基　　金：甘肃省科技重大专项(1502FKDA008)。

摘　　要：目的探讨不同培养基对抗破伤风毒素人源单抗工程细胞株生长状态及抗体关键质量属性的影响,筛选出适应抗破伤风毒素人源单抗工程细胞株的培养基。方法选取Growth A、Dynamis、T543种商用培养基,采用Fed-batch培养模式培养,观察活细胞密度及细胞活率;并通过SEC-HPLC和CE-SDS分析抗体纯度、cIEF法分析pI及电荷异构体。结果Growth A medium培养的细胞活细胞密度最高,细胞活率在Dynamis medium和T54 medium之间;Growth A medium培养的细胞抗体纯度最高;3种培养基培养的细胞抗体pI差异不明显;Growth A medium培养的细胞抗体电荷变异体酸性峰数量和占比均少于其他两种培养基,主峰占比在其他两种培养基之间。结论Growth A medium较适合抗破伤风毒素人源单抗工程细胞株的培养。Objective To investigate the effects of different media on growth of engineered cell strain and critical quality attributes of human monoclonal antibody(McAb)against tetanus toxin and screen the optimal medium.Methods Three commercial culture media,Growth A,Dynamis and T54,were used in fed-batch model,and the cell viability and viable cell density were determined.The antibody purity were analyzed by SEC-HPLC and CE-SDS,while the isoelectric point and charge heterogeneity by cIEF method.Results The viable cell density in Growth A medium was higher than,while the cell viability rate was between,those in Dynamis and T54 media.The purity of McAb in Growth A medium was higher than those in the other two media.However,there was no significant difference in the PI values of McAbs cultured in the three media.The number and proportion of acid peak of charge variation of antibody cultured in Growth A medium were less than,while the proportion of main peak was between,those in the other two media.Conclusion Growth A medium is more suitable for the cultivation of engineered cells for McAb against tetanus toxin.

关 键 词：细胞培养基 破伤风毒素 单克隆抗体 质量属性 

分 类 号：R373.2[医药卫生—病原生物学]