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SEC Based Method for Size Determination of Immune Complexes of Therapeutic Antibodies in Animal Matrix

机译:基于SEC的动物基质中治疗性抗体免疫复合物大小的测定方法

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摘要

Therapeutic monoclonal antibodies (mAbs) represent a milestone in pharmacological development. Their superiority is based on the combination of high specificity, low toxicity, and long half-life that characterizes biologics. If biologics have Achilles' heel, it is their potential immunogenicity. To better understand the impact of the size of immune complexes of mAbs on anti-drug antibody (ADA) dependent adverse reactions in Macaca fascicularis, we developed an efficient high-throughput size exclusion chromatography- (SEC-) based methodology that enables analysis of the size, size distribution, and ratio of free and ADA-complexed mAb in serum allowing for assessment of formation and clearance of circulating ADA-mAb immune complexes (CIC).
机译:治疗性单克隆抗体(mAbs)代表了药理学发展的一个里程碑。它们的优越性是生物制剂具有的高特异性,低毒性和长半衰期的结合。如果生物制剂具有致命弱点,那就是其潜在的免疫原性。为了更好地了解单克隆抗体免疫复合物的大小对猕猴的抗药物抗体(ADA)依赖性不良反应的影响,我们开发了一种有效的基于高通量大小排阻色谱法(SEC-)的方法,可以分析血清中游离和ADA复合mAb的大小,大小分布以及比例,从而可以评估循环ADA-mAb免疫复合物(CIC)的形成和清除。

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