Biomolecular Measurement Division, National Institute of Standards and Technology, Gaithersburg, MD 20899, USA.
Institute for Bioscience and Biotechnology Research, Rockville, MD 20850, USA.
Sci Rep. 2017 Feb 10;7:42497. doi: 10.1038/srep42497.
Using mAbs as therapeutic molecules is complicated by the propensity of mAbs to aggregate at elevated concentrations, which can lead to a variety of adverse events in treatment. Here, we describe a proof-of-concept for new methodology to detect and quantify mAb aggregation. Assay development included using an aggregated mAb as bait for screening of phage display peptide library and identifying those peptides with random sequence which can recognize mAb aggregates. Once identified, the selected peptides can be used for developing quantitative methods to assess mAb aggregation. Results indicate that a peptide binding method coupled with mass spectrometric detection of bound peptide can quantify mAb aggregation and potentially be useful for monitoring aggregation propensity of therapeutic protein candidates.
使用单克隆抗体作为治疗分子很复杂，因为单克隆抗体在高浓度下容易聚集，这可能导致治疗中出现各种不良反应。在这里，我们描述了一种新方法的概念验证，用于检测和定量单克隆抗体聚集。该方法的开发包括使用聚集的单克隆抗体作为筛选噬菌体展示肽文库的诱饵，并鉴定那些具有随机序列的肽可以识别单克隆抗体聚集物。一旦被鉴定出来，所选的肽可以用于开发定量方法来评估单克隆抗体的聚集。结果表明，一种与肽结合方法相结合的肽结合方法，结合质谱检测结合的肽，可以定量单克隆抗体聚集，并且可能有助于监测治疗性蛋白候选物的聚集倾向。
