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使用单克隆抗体作为测量抗阿达木单抗抗体的国际标准。

Using monoclonal antibodies as an international standard for the measurement of anti-adalimumab antibodies.

作者信息

van Schouwenburg Pauline A, Kruithof Simone, Wolbink Gertjan, Wouters Diana, Rispens Theo

机构信息

Department of Immunopathology, Sanquin Research and Landsteiner Laboratory Academic Medical Centre, Amsterdam, The Netherlands.

Department of Immunopathology, Sanquin Research and Landsteiner Laboratory Academic Medical Centre, Amsterdam, The Netherlands; Jan van Breemen Research Institute, Reade, Amsterdam, The Netherlands.

出版信息

J Pharm Biomed Anal. 2016 Feb 20;120:198-201. doi: 10.1016/j.jpba.2015.12.040. Epub 2015 Dec 28.

Abstract

Comparing studies investigating anti-drug antibody (ADA) formation is hampered by the lack of comparability between study protocols, assay formats, and standardized reference materials. In this respect, the use of an international standard would mean a major step forward. Here we compared 11 fully human monoclonal antibodies against adalimumab in two assays commonly used for ADA measurement; the bridging ELISA and the antigen binding test (ABT). Our results show non-parallel titration of the monoclonal antibodies in both assays, which we also find for polyclonal ADA sources. Moreover, we observed that the output of the bridging ELISA depends to a large degree on the affinity of the monoclonal antibody. For the ABT, results reflect a combination of affinity and avidity. This suggests that rather than reporting ADA values in nanogram per milliliter, arbitrary units may be more appropriate. Together our data highlight the difficulty of ADA standardization by identifying several pitfalls that should be taken into account when selecting a standard for ADA testing.

摘要

由于研究方案、检测形式和标准化参考材料之间缺乏可比性,比较研究抗药物抗体(ADA)形成的相关研究受到阻碍。在这方面,使用国际标准将意味着向前迈出一大步。在此,我们在两种常用于ADA测量的检测方法中比较了11种抗阿达木单抗的全人单克隆抗体;桥接ELISA和抗原结合试验(ABT)。我们的结果表明,在这两种检测方法中,单克隆抗体的滴定均不平行,我们在多克隆ADA来源中也发现了这种情况。此外,我们观察到桥接ELISA的结果在很大程度上取决于单克隆抗体的亲和力。对于ABT,结果反映了亲和力和avidity的综合情况。这表明,与其以每毫升纳克报告ADA值,任意单位可能更合适。我们的数据共同强调了ADA标准化的困难,通过识别在选择ADA检测标准时应考虑的几个陷阱。

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