摘要
随着大量生物技术药物的研发,生物技术药物的评价越来越受到重视。与传统小分子药物不同,生物技术药物在体内产生的抗药抗体(ADA)可能会中和药物的活性,造成在非临床和临床研究中观察到的效应并非药物真正的药理和毒性反应,因此需要对药物的免疫原性进行评价。通过检测ADA可评价药物的免疫原性。检测ADA的主要干扰物质为药物本身。目前,最广泛使用的桥联ELISA无法检测药物-ADA复合物,会导致假阴性结果,影响检测的准确度。药物耐受作为免疫原性检测方法学验证中的一项重要指标,应尽可能减少游离药物的干扰,客观反映体内ADA水平。因此,恰当的样品前处理是测定结果准确性的关键。目前已报道的前处理方法有液相ELISA、酸处理、沉淀与酸解离、磁珠提取与酸解离和磁珠提取与热解离等,这些方法均有助于减少药物干扰,改善药物耐受。
With the development of many biotechnology drugs,the evaluation of biotechnology drugs has received more attention.Unlike traditional small molecule drugs,biotechnological drugs can produce anti-drug antibodies(ADAs)in the body that may neutralize the activity of drugs so that the effects observed in non-clinical and clinical studies are not the true pharmacological and toxical effects of drugs,hence the need to evaluate the immunogenicity of drugs,possibly by detecting ADAs.The main interfering substances detected by ADAs are usually derived from the drug itself.The most widely used bridging ELISA is currently unable to detect the drug-ADA complex,which leads to the false negative results in the test and affects the accuracy of the results.Drug tolerance is an important indicator in the validation of immunogenicity assay.It is important to minimize the interference of free drugs and objectively reflect the level of ADAs in the body.Therefore,proper sample preparation is the key to accurate measurement results.The pretreatment methods that have been reported include solutionELISA,acid treatment,precipitation and acid dissociation,bead extraction and acid dissociation,beadextraction and heat-dissociation.They can help reduce drug interference and improve drug tolerance.
作者
陈沛卓
洛文靖
程远国
任欣怡
CHEN Pei-zhuo;LUO Wen-jing;CHENG Yuan-guo;REN Xin-yi(School of Pharmacy,Fudan University,Shanghai 201203,China;Shanghai InnoStar Bio-tech Co.,Ltd.,Shanghai 201203,China;China Stata Institute of Pharmaceutical Industry,Shanghai 201203,China)
出处
《中国药理学与毒理学杂志》
CAS
北大核心
2021年第1期72-76,共5页
Chinese Journal of Pharmacology and Toxicology
基金
国家科技重大专项(2019ZX09732001-020)。
关键词
生物技术药物
免疫原性
抗药抗体
耐药性
biotechnology drugs
immunogenicity
anti-drug antibodies
drug tolerance
