植物平台生产单克隆抗体的优化策略  

The optimization strategies for the production of monoclonal antibodies on plant platforms

作　　者：陈子晴 刘德 于荣敏[1] 朱建华[1] CHEN Ziqing;LIU De;YU Rongmin;ZHU Jianhua(Biotechnological Institute of Chinese Materia Medica,Jinan University,Guangzhou 511400,China)

机构地区：[1]暨南大学中药生物技术研究所,广州511400

出　　处：《生命的化学》2024年第7期1205-1215,共11页Chemistry of Life

基　　金：山东省重点研发计划项目(2022SFGC0105);广州市科技计划项目(2023A03J0613);广东省自然科学基金项目(2024A1515010301)。

摘　　要：治疗性单克隆抗体主要为免疫球蛋白G(immunoglobulin G,IgG)。作为重组蛋白生物药物,IgG具有广泛的临床适应性。植物平台为治疗性重组蛋白的生产提供了快速、灵活和易于扩展的替代平台,在个性化治疗蛋白的生产和流行性疾病药物开发时期受到广泛关注。由于单克隆抗体在生产过程中容易受到多种翻译后修饰途径的影响,植物平台生产的重组单克隆抗体可能存在微观异质性,从而影响抗体的稳定性、生物活性或引起不必要的免疫原性。本文就以下两方面展开综述:植物平台中特异性β-1,2-木糖和核心α-1,3-岩藻糖的消除、β-1,4-半乳糖基化途径的引入和其他糖基化修饰方式的修改等优化策略进展;植物源重组抗体表达体系、培养体系和下游加工方式的优化策略进展,以提高植物源单抗的有效性、安全性和生产条件。The major component of therapeutic monoclonal antibodies is mainly immunoglobulin G(IgG),which has broad clinical indications as recombinant protein biopharmaceuticals.Plant-based platforms offer fast,flexible and easily scalable alternative platforms for the production of therapeutic recombinant proteins and have received much attention during the production of personalized therapeutic proteins and the period of drug development for pandemic diseases.Due to the susceptibility of monoclonal antibodies to multiple posttranslational modification pathways during production,recombinant monoclonal antibodies produced by plantbased platforms may have microscopic heterogeneity,which may affect the stability,bioactivity,or unintended immunogenicity of the antibodies.In order to improve the efficiency,security,and yield of plant-derived monoclonal antibodies,this paper reviewed the following two aspects of related developments.First,we talked about the optimization strategies such as the removal of specificβ-1,2-xylose and coreα-1,3-fucose,the introduction ofβ-1,4-galactosylation pathway,and the modification of other glycosylation modifications in plant platforms.Then,research progresses in optimization strategies of plant-derived recombinant antibody expression system,culture system,and downstream processing methods were discussed.

关 键 词：植物平台 重组蛋白 单克隆抗体 植物糖工程 生产优化 

分 类 号：Q789[生物学—分子生物学]