蛋白药降免疫原性改造策略  

Immunogenicity mitigation strategies of protein drugs

作　　者：李庆斯 包准 周晓 张雷[1,3] LI Qingsi;BAO Zhun;ZHOU Xiao;ZHANG Lei(Department of Biochemical Engineering,School of Chemical Engineering and Technology,Tianjin University,Tianjin 300350,China;Department of Pharmaceutical Engineering,School of Chemical Engineering and Technology,Tianjin University,Tianjin 300350,China;Frontier Science Center for Synthetic Biology and Key Laboratory of Systems Bioengineering(MOE),Tianjin University,Tianjin 300350,China)

机构地区：[1]天津大学化工学院生物化工系,天津300350 [2]天津大学化工学院制药工程系,天津300350 [3]天津大学教育部合成生物学前沿科学中心,系统生物工程教育部重点实验室,天津300350

出　　处：《石油化工》2024年第8期1196-1204,共9页Petrochemical Technology

基　　金：国家重点研发计划(2022YFC2104801);国家自然科学基金项目(22208240)。

摘　　要：蛋白药是一种生物活性大分子,可高效治疗多种疾病,近年来在生物医疗领域受到了广泛关注。然而,由于免疫原性的问题,蛋白药很容易被患者的免疫系统快速清除。因此,降低免疫原性对于蛋白药的发展至关重要。讨论了影响免疫原性的主要因素以揭示其背后的机制;综述了多种降免疫原性的策略,包括聚乙二醇化、两性离子化、糖基化以及蛋白质融合等;对未来蛋白药的发展趋势进行了展望。Protein drugs are bioactive macromolecules and can effectively treat many diseases.They have drawn great attention from the biomedicalfield in recent years.However,because of the immunogenicity problem,protein drugs can be rapidly removed by the immune system of patients.Therefore,reducing immunogenicity is critical for the development of protein drugs.In this review,the main factors affecting immunogenicity were discussed to reveal the potential mechanisms.The immunogenicity mitigation strategies were elaborated,including PEGylation,zwitterlation,glycosylation,and protein fusion.Finally,the future development of protein drugs was predicted.

关 键 词：蛋白药 免疫原性 两性离子材料 融合蛋白 

分 类 号：TQ93[化学工程]