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

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 include...

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Autores principales: Cheung, Crystal S. F., Anderson, Kyle W., Patel, Pooja M., Cade, Keale L., Phinney, Karen W., Turko, Illarion V.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5301252/
https://www.ncbi.nlm.nih.gov/pubmed/28186164
http://dx.doi.org/10.1038/srep42497
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author Cheung, Crystal S. F.
Anderson, Kyle W.
Patel, Pooja M.
Cade, Keale L.
Phinney, Karen W.
Turko, Illarion V.
author_facet Cheung, Crystal S. F.
Anderson, Kyle W.
Patel, Pooja M.
Cade, Keale L.
Phinney, Karen W.
Turko, Illarion V.
author_sort Cheung, Crystal S. F.
collection PubMed
description 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.
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spelling pubmed-53012522017-02-15 A new approach to quantification of mAb aggregates using peptide affinity probes Cheung, Crystal S. F. Anderson, Kyle W. Patel, Pooja M. Cade, Keale L. Phinney, Karen W. Turko, Illarion V. Sci Rep Article 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. Nature Publishing Group 2017-02-10 /pmc/articles/PMC5301252/ /pubmed/28186164 http://dx.doi.org/10.1038/srep42497 Text en Copyright © 2017, The Author(s) http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
spellingShingle Article
Cheung, Crystal S. F.
Anderson, Kyle W.
Patel, Pooja M.
Cade, Keale L.
Phinney, Karen W.
Turko, Illarion V.
A new approach to quantification of mAb aggregates using peptide affinity probes
title A new approach to quantification of mAb aggregates using peptide affinity probes
title_full A new approach to quantification of mAb aggregates using peptide affinity probes
title_fullStr A new approach to quantification of mAb aggregates using peptide affinity probes
title_full_unstemmed A new approach to quantification of mAb aggregates using peptide affinity probes
title_short A new approach to quantification of mAb aggregates using peptide affinity probes
title_sort new approach to quantification of mab aggregates using peptide affinity probes
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5301252/
https://www.ncbi.nlm.nih.gov/pubmed/28186164
http://dx.doi.org/10.1038/srep42497
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