WAVE25生物反应器对白细胞介素-12表达的工艺放大  

Scale-up of procedure for interleukin-12 expression by using WAVE25 bioreactor

作　　者：乔磊 郑彬彬 杨盼盼 陈文成 闫乐乐 王建刚 吴明远 QIAO Lei;ZHENG Bin-bin;YANG Pan-pan;CHEN Wen-cheng;YAN Le-le;WANG Jian-gang;WU Ming-yuan(Kanglitai Biomedical(Qingdao)Co.LTD,Qingdao 266000,Shandong Province,China)

机构地区：[1]康立泰生物医药(青岛)有限公司,山东青岛266000

出　　处：《中国生物制品学杂志》2022年第4期475-480,共6页Chinese Journal of Biologicals

基　　金：国家科技重大专项“重大新药创制”(2017ZX09303017);山东省重大科技创新工程项目(2018CXGC1404)。

摘　　要：目的 利用WAVE25生物反应器进行白细胞介素-12(interleukin-12,IL-12)表达的工艺放大,为后期的大规模工业化生产提供参考。方法 采用BIOSTAT B 10 L生物反应器和GE WAVE25 50 L生物反应器进行IL-12表达的工艺放大,依据细胞活率、密度、pH及葡萄糖、乳酸、铵根离子、谷氨酰胺等生长代谢参数对工艺放大过程中间控制进行监测,依据SDS-PAGE、蛋白产量、等电点、肽图等理化检测指标对表达产物进行初步质量检测和鉴定。结果 工艺放大前后中间过程控制参数变化曲线及表达产物的质量指标均一致,各参数均在质量标准范围内。结论 该表达工艺可从BIOSTAT B 10 L生物反应器到GE WAVE25 50 L稳健放大,为后续更大规模的工业化生产提供了参考。Objective To scale up the procedure for interleukin-12(IL-12) expression and provide a reference for subsequent large-scale industrial production. Methods The procedure for IL-12 expression was scaled-up by using BIOSTAT B 10 L and GE WAVE25 50 L bioreactors respectively. Based on the growth and metabolic parameters such as cell living rate,density,pH,glucose,lactic acid,ammonium ions and glutamine,the intermediate control in course of scale-up was monitored. Primary control tests were performed on the expressed product based on physical and chemical testing indexes such as SDS-PAGE,yield of product,isoelectric point and peptide map. Results The change curves of intermediate process control parameters and the quality indexes of expressed products before and after scale-up were in agreement,all of which were within the range of quality standard. Conclusion The procedure may be steadily scaled-up from BIOSTAT B 10 L to GE WAVE25 50 L bioreactors,which provides a reference for subsequent large-scale industrial production.

关 键 词：生物反应器 白细胞介素-12 工艺放大 

分 类 号：R979.1[医药卫生—药品]