色谱2024，Vol.42Issue(6)：533-543,11.DOI:10.3724/SP.J.1123.2023.12010
色谱技术在抗体分离纯化中的应用进展
Recent progress of chromatographic techniques for antibody purification
摘要
Abstract
Antibody drugs are becoming increasingly popular in disease diagnosis,targeted therapy,and immunoprevention owing to their characteristics of high targeting ability,strong specificity,low toxicity,and mild side effects.The demand for antibody drugs is steadily in-creasing,and their production scale is expanding.Upstream cell culture technology has been greatly improved by the high-capacity production of monoclonal antibodies.However,the downstream purification of antibodies presents a bottleneck in the production process.Moreover,the purification cost of antibodies is extremely high,accounting for approximately 50％-80％of the total cost of antibody production.Chromatographic technology,given its se-lectivity and high separation efficiency,is the main method for antibody purification.This process usually involves three stages:antibody capture,intermediate purification,and polis-hing.Different chromatographic techniques,such as affinity chromatography,ion-exchange chromatography,hydrophobic interaction chromatography,mixed-mode chromatography,and temperature-responsive chromatography,are used in each stage.Affinity chromatography,mainly protein A affinity chromatography,is applied for the selective capture and purification of antibodies from raw biofluids or harvested cell culture supernatants.Other chromatographic techniques,such as ion-exchange chromatography,hydrophobic interaction chromatography,and mixed-mode chromatography,are used for intermediate purification and antibody polishing.Affinity biomimetic chromatography and hydrophobic charge-induction chromatography can produce antibodies with purities comparable with those obtained through protein A chromatog-raphy,by employing artificial chemical/short peptide ligands with good selectivity,high stabili-ty,and low cost.Temperature-responsive chromatography is a promising technique for the sep-aration and purification of antibodies.In this technique,antibody capture and elution is con-trolled by simply adjusting the column temperature,which greatly eliminates the risk of anti-body aggregation and inactivation under acidic elution conditions.The combination of different chromatographic methods to improve separation selectivity and achieve effective elution under mild conditions is another useful strategy to enhance the yield and quality of antibodies.This re-view provides an overview of recent advances in the field of antibody purification using chroma-tography and discusses future developments in this technology.关键词
抗体/色谱技术/分离纯化/亲和色谱/混合模式色谱/温敏色谱/综述Key words
antibody/chromatographic techniques/separation and purification/affinity chro-matography/mixed-mode chromatography/temperature-responsive chromatography/review分类
化学化工引用本文复制引用
刘家玮,唐长伟,夏一然,白泉..色谱技术在抗体分离纯化中的应用进展[J].色谱,2024,42(6):533-543,11.基金项目
国家自然科学基金(22174108,21874106) （22174108,21874106）
陕西省自然科学基金(2021JM-310).National Natural Science Foundation of China(Nos.22174108,21874106) （2021JM-310）
Natural Science Foundation of Shaanxi Province(No.2021JM-310). （No.2021JM-310）
