适应高滴度抗体制备的抗体捕集纯化技术研究进展  

Antibody capture technologies for high-titer antibody production

作　　者：史清洪[1,2] 孙彦[1,2] SHI Qinghong;SUN Yan(School of Chemical Engineering and Technology, Tianjin University, Tianjin 300350,China;Key Laboratory of SystemsBioengineering (Ministry of Education), Tianjin 300350, China)

机构地区：[1]天津大学化工学院,天津300350 [2]系统生物工程教育部重点实验室,天津300350

出　　处：《化工进展》2019年第1期576-585,共10页Chemical Industry and Engineering Progress

基　　金：国家自然科学基金面上项目(21476166;21878221);国家自然科学基金创新群体项目(21621004);国家自然科学基金重点项目(21236005)

摘　　要：抗体捕集纯化是单克隆抗体和Fc融合蛋白药物制备过程的关键步骤。但相较于大规模动物细胞培养技术的迅猛发展,抗体的捕集纯化已经成为了制约单抗药物生产的主要"瓶颈"。本文回顾了蛋白A亲和层析和阳离子交换层析等当前抗体药物工业生产过程主要捕集纯化技术的发展现状和应用情况,介绍了近年来亲和肽层析和混合模式吸附层析等新型层析分离技术的发展以及膨胀床吸附和多柱串联吸附等过程集成方法在提高抗体捕集效率方面所展现的良好前景。在此基础上,指出了影响抗体捕集纯化的主要因素以及各技术发展中存在的问题,展望抗体捕集纯化技术的发展方向。Product capture from a cell culture broth is a key step in the production of antibodies and Fcfusion proteins.With a rapid increase of large-scale animal cell culture techniques,capture techniques in antibody production have become the key technical bottleneck in monoclonal antibody productions.In this paper,core antibody capture methods,including protein A chromatography and cation exchange chromatography,have been reviewed in term of their history and applications.At the same time,peptide affinity chromatography,mixed-mode or multimodal chromatography,expanded-bed adsorption and sequential multi-column adsorption have been introduced to exhibit their great potentials in highefficient antibody captures.Moreover,the factors affecting the capture and purification processes were analyzed while the problems that need to be solved to improve the technologies were discussed.Finally,perspectives into the development of antibody captures were discussed with focusing on the technological aspects of the chromatographic methods.

关 键 词：抗体 捕集纯化 蛋白A层析 阳离子交换层析 亲和肽层析 混合模式层析 膨胀床吸附 多柱串联吸附 

分 类 号：TQ028.8[化学工程]