治疗性单克隆抗体类药物分析技术及其应用  

Analysis technology and application progress of therapeutic monoclonal antibody drugs

作　　者：张国林 景荣先[2] 郭乐[3] 邢以文 薛满 ZHANG Guo-lin;JING Rong-xian;GUO Le;XING Yi-wen;XUE Man(Suzhou Institute for Drug Control,Suzhou 215000,China;Suzhou Municipal Hospital,Suzhou 215000,China;Ningxia Medical University,Yinchuan 750004,China)

机构地区：[1]苏州市药品检验检测研究中心,苏州215000 [2]苏州市立医院,苏州215000 [3]宁夏医科大学,银川750004

出　　处：《中国新药杂志》2021年第6期528-534,共7页Chinese Journal of New Drugs

基　　金：江苏省市场监督管理局科技项目(KJ207561);苏州市科技发展计划资助项目(SYS201425)。

摘　　要：治疗性单克隆抗体(单抗)类药物是高度均一的生物大分子,抗原表位、理化性质和生物活性等方面的均一性程度高,能够通过特异性地与靶标分子结合发挥治疗作用。单抗类药物治疗过程中不良反应发生率低、患者耐受性高。单抗类药物是生物药物领域的热点和焦点,已成为现代生物制药行业中占比最大、增长最快的细分领域。根据生产技术和工艺的不同,单抗类药物发展已经经历了4代。我国最近批准上市的信迪利单抗注射液、特瑞普利单抗注射液、注射用卡瑞利珠单抗和替雷利珠单抗注射液等均属于第3代人源化单克隆抗体药物。单抗类药物分子结构复杂,容易发生二聚体、多聚体、末端氨基酸突变等不均一性变化,严重影响临床用药的安全性和有效性。对单抗类药物的原液和成品进行有效的质量控制是确保该类产品安全性和有效性的重要措施。目前,单抗类产品质量控制与分析的主要方法包括高效液相色谱(HPLC)法、酶联免疫吸附测定(ELISA)法、毛细管区带电泳(CZE)法、毛细管等电聚焦电泳(cIEF)法、成像毛细管等电聚焦电泳(iCIEF)法和十二烷基硫酸钠-毛细管电泳(CE-SDS)法等。本文就单抗类药物质量控制分析方法及应用进行综述,为相关研究及产品质量控制提供参考。Therapeutic monoclonal antibody(mAb)drugs are highly homogeneous bio-macromolecules,with high degree of homogeneity in antigen epitopes,physical and chemical properties and biological activities,which can specifically bind to the target molecules.In the course of treatment,the incidence of adverse reactions is low while the tolerance of patients is high.Monoclonal antibodies are the focus in the field of bio-pharmaceutics,which have become the most important and fastest growing area in modern biopharmaceutical industry.According to the different production process and technology,the development of monoclonal antibodies has experienced four generations.Sintilimab injection,treprizumab injection,carrizumab for injection and tirizumab injection recently approved in China are all the third generation of humanized monoclonal antibody drugs.The molecular structure of monoclonal antibody drugs is complex,which is easy to change the heterogeneity of dimer,polymer and terminal amino acid mutation.These changes may cause serious effects on the safety and effectiveness of clinical medication.It is an important measure to control the quality of the original and finished products of monoclonal anti-tumor drugs to ensure the safety and effectiveness of such products.At present,the main methods of quality control and analysis of monoclonal antibody products include HPLC,ELISA,CZE,cIEF,iCIEF and CE-SDS.In this paper,the analysis methods for quality control and application status of monoclonal antibodies were reviewed,which can provide reference for related research and product quality control.

关 键 词：单克隆抗体 高效液相色谱法 酶联免疫吸附测定法 毛细管区带电泳法 细管等电聚焦电泳法 十二烷基硫酸钠-毛细管电泳 

分 类 号：R979.1[医药卫生—药品]