A Surface Plasmon Resonance-based assay to measure serum concentrations of therapeutic antibodies and anti-drug antibodies
A Surface Plasmon Resonance-based assay to measure serum concentrations of therapeutic antibodies and anti-drug antibodies
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DOI：
10.1038/s41598-018-37950-4
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发表时间：
2019-02-14
影响因子：
4.6
通讯作者：
Gobbi, Marco
中科院分区：
文献类型：
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作者：
Beeg, Marten;Nobili, Alessandro;Gobbi, Marco
治疗药物和免疫原性监测（TDIM）越来越多地被提议用于指导生物制剂治疗，其特征在于其血液水平的高度个体间变异性，以允许对无应答者的管理做出客观决策，并减少这些昂贵治疗的不必要干预。然而，TDIM尚未进入临床实践，部分原因是酶联免疫吸附测定（ELISA）的准确性和精密度的不确定性。在这里，我们报告了一种新的表面等离子体共振（SPR）为基础的TDIM，适用于测量血清浓度的英夫利西单抗，抗肿瘤坏死因子α（抗TNF α）的抗体，和抗英夫利西单抗抗体的特性。SPR具有明显的优势，可以在几分钟内直接检测和测量血清抗体，避免了迄今为止提出的方法的长时间孵育/分离/洗涤/检测步骤，降低了复杂性和可变性。此外，可以同时测量药物和抗药物抗体。这种新方法的灵敏度和重现性进行了验证，并显示出比商业ELISA试剂盒的成本效益。该方法可用于其他生物治疗。这些数据为开发基于SPR的床旁设备进行快速现场分析铺平了道路。
Therapeutic drug and immunogenicity monitoring (TDIM) is increasingly proposed to guide therapy with biologics, characterised by high inter-individual variability of their blood levels, to permit objective decisions for the management of non-responders and reduce unnecessary interventions with these expensive treatments. However, TDIM has not yet entered clinical practice partly because of uncertainties regarding the accuracy and precision of enzyme-linked immunosorbent assays (ELISA). Here we report the characterisation of a novel surface plasmon resonance (SPR)-based TDIM, applied to the measurement of serum concentrations of infliximab, an antibody against tumour necrosis factor a (anti-TNF alpha), and anti-infliximab antibodies. SPR has the obvious advantages of directly detecting and measuring serum antibodies in minutes, avoiding the long incubation/separation/washing/detection steps of the methods proposed so far, reducing complexity and variability. Moreover, drug and anti-drug antibodies can be measured simultaneously. This new method was validated for sensitivity and reproducibility, and showed cost-effectiveness over commercial ELISA kits. This method may be applied to other biotherapeutics. These data pave the way for the development of SPR-based point-of-care devices for rapid on-site analysis.