A new approach to quantification of mAb aggregates using peptide affinity probes

被引:0
作者
Crystal S. F. Cheung
Kyle W. Anderson
Pooja M. Patel
Keale L. Cade
Karen W. Phinney
Illarion V. Turko
机构
[1] National Institute of Standards and Technology,Biomolecular Measurement Division
[2] Institute for Bioscience and Biotechnology Research,undefined
来源
Scientific Reports | / 7卷
关键词
D O I
暂无
中图分类号
学科分类号
摘要
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.
引用
收藏
相关论文
共 89 条
[1]  
Lowe D(2011)Aggregation, stability, and formulation of human antibody therapeutics Adv. Protein Chem. Struct. Biol. 84 41-61
[2]  
Singh SK(2011)Impact of product-related factors on immunogenicity of therapeutics J. Pharm. Sci. 100 354-387
[3]  
Rosenberg AS(2006)Effects of protein aggregates: an immunologic perspective AAPS J. 8 E501-E507
[4]  
Cromwell MEM(2006)Protein aggregation and bioprocessing AAPS J. 8 E572-E579
[5]  
Hilario E(2011)Aggregates in monoclonal antibody manufacturing processes Biotechnol. Bioeng. 108 1494-1508
[6]  
Jacobson F(2010)Phase separation of an IgG1 antibody solution under a low ionic strength condition Pharm. Res. 27 1348-1360
[7]  
Vazquez-Rey M(2010)Stability of protein pharmaceuticals: an update Pharm. Res. 27 544-575
[8]  
Lang DA(2014)Improving monoclonal antibody selection and engineering using measurements of colloidal protein interactions J. Pharm. Sci. 103 3356-3363
[9]  
Nishi H(2015)Accelerated formulation development of monoclonal antibodies (mAbs) and mAb-based modalities: review of methods and tools J. Biomol. Screen. 20 468-483
[10]  
Manning. MC(2015)Hydrogen exchange mass spectrometry reveals protein interfaces and distant dynamic coupling effects during the reversible self-association of an IgG1 monoclonal antibody mAbs 7 525-539