抗体类药物超敏反应研究进展  

Research progress on hypersensitivity reactions induced by monoclonal antibody products

作　　者：宫新江 邵雪 张旻 朱飞鹏[1] 闫莉萍[1] 于冰 叶旋 刘轶博 周植星 崔岚 赵华琛 王庆利[1] 王海学[1] GONG Xin-jiang;SHAO Xue;ZHANG Min;ZHU Fei-peng;YAN Li-ping;YU Bing;YE Xuan;LIU Yi-bo;ZHOU Zhi-xing;CUI Lan;ZHAO Hua-chen;WANG Qing-li;WANG Hai-xue(Center for Drug Evaluation,NMPA,Beijing 100022,China)

机构地区：[1]国家药品监督管理局药品审评中心

出　　处：《中国新药杂志》2019年第21期2651-2657,共7页Chinese Journal of New Drugs

基　　金：国家“重大新药创制”科技重大专项资助项目(2014ZX09102041)

摘　　要：抗体类药物在临床应用中很可能导致不同类型的超敏反应(hypersensitivity reaction,HSR)。在近期某些创新单抗或双功能抗体的非临床研究中,相关动物种属或人源化动物模型给予候选分子也常见非预期HSR,严重时可能对药效学、药动学和/或毒理学研究结果的解读和评价以及人体不良反应的预测造成干扰。探索HSR发生的机制有助于科学分析非临床研究的结果,并对临床试验中人体用药风险的评估和相应的风险缓解策略的制定提供更有价值的参考信息。本文对抗体类药物导致的HSR类型、临床表现和诊断方法、可能的发生机制进行了综述,并对非临床研究中HSR相关标志物的检测方法和必要性进行了探讨,以供研究者和监管机构关注或参考。Monoclonal antibody products have relatively high incidence to induce various types of hypersensitivity reactions(HSR) in clinical practice. For some recent innovative monoclonal or bifunctional antibodies,unexpected HSR are also encountered in non-clinical studies. In some cases,HSR may interfere with the interpretation and evaluation of research results of pharmacodynamics,pharmacokinetics and/or toxicity,as well as the prediction of potential adverse effects,in humans. Investigation on the possible mechanisms of HSR is helpful for reasonable interpretation on the findings of non-clinical studies and providing highly valuable reference information on prediction of potential risks to subjects in clinical trials and risk mitigation strategies. In this article,the types,clinical manifestations,diagnostic methods and possible mechanisms of monoclonal antibody products-induced HSR were reviewed. The assay methods and necessity of HSR-related biomarkers in non-clinical studies were also discussed.It is hoped that this review could draw the attentions of researchers and regulators to this issues and provide significant reference.

关 键 词：抗体类药物 超敏反应 非临床研究 临床试验 机制 

分 类 号：R965.3[医药卫生—药理学]