Label-free shotgun proteomics: Exploiting a reliable and sensitive method to monitor residual host-cell proteins in monoclonal antibody products

The removal of host cell proteins (HCPs) remains a challenge in the downstream processing of monoclonal antibodies (mAbs). It is critical to monitor residual HCPs since they can have an impact on product stability and safety. The enzyme-linked immunosorbent assay (ELISA) only quantifies the total am...

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Main Authors: Somar Khalil, Adeline Wychowski, Cyrille Chéry, Annick Gervais
Format: Article
Language:English
Published: Elsevier 2023-06-01
Series:Journal of Pharmaceutical and Biomedical Analysis Open
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Online Access:http://www.sciencedirect.com/science/article/pii/S2949771X23000129
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author Somar Khalil
Adeline Wychowski
Cyrille Chéry
Annick Gervais
author_facet Somar Khalil
Adeline Wychowski
Cyrille Chéry
Annick Gervais
author_sort Somar Khalil
collection DOAJ
description The removal of host cell proteins (HCPs) remains a challenge in the downstream processing of monoclonal antibodies (mAbs). It is critical to monitor residual HCPs since they can have an impact on product stability and safety. The enzyme-linked immunosorbent assay (ELISA) only quantifies the total amount of HCPs and does not indicate the identity or quantity of any specific HCP. Mass spectrometry-based proteomics applications demonstrate an advantage in quantitatively profiling individual HCPs. However, technical reproducibility, dynamic range, and ensuring an acceptable statistical significance of scoring measurements are critical hurdles that ought to be overcome. In this paper, we describe a sensitive and reproducible shotgun proteomics approach that includes an efficient mAb depletion strategy and addresses the shortcomings of such workflows. Our methodology is potentially a valuable complement or alternative to ELISA. Additionally, it can facilitate the purification process development and the evaluation of ELISA kits upon process changes.
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institution DOAJ
issn 2949-771X
language English
publishDate 2023-06-01
publisher Elsevier
record_format Article
series Journal of Pharmaceutical and Biomedical Analysis Open
spelling doaj-art-9b379f6a9d204c34a5dc595302f2fa392025-08-20T02:51:38ZengElsevierJournal of Pharmaceutical and Biomedical Analysis Open2949-771X2023-06-01110001210.1016/j.jpbao.2023.100012Label-free shotgun proteomics: Exploiting a reliable and sensitive method to monitor residual host-cell proteins in monoclonal antibody productsSomar Khalil0Adeline Wychowski1Cyrille Chéry2Annick Gervais3Correspondence to: Chemin du Foriest 1, Braine L’Alleud 1420, Belgium.; Department of Analytical Science Biologicals, UCB, Braine L’Alleud, BelgiumDepartment of Analytical Science Biologicals, UCB, Braine L’Alleud, BelgiumDepartment of Analytical Science Biologicals, UCB, Braine L’Alleud, BelgiumDepartment of Analytical Science Biologicals, UCB, Braine L’Alleud, BelgiumThe removal of host cell proteins (HCPs) remains a challenge in the downstream processing of monoclonal antibodies (mAbs). It is critical to monitor residual HCPs since they can have an impact on product stability and safety. The enzyme-linked immunosorbent assay (ELISA) only quantifies the total amount of HCPs and does not indicate the identity or quantity of any specific HCP. Mass spectrometry-based proteomics applications demonstrate an advantage in quantitatively profiling individual HCPs. However, technical reproducibility, dynamic range, and ensuring an acceptable statistical significance of scoring measurements are critical hurdles that ought to be overcome. In this paper, we describe a sensitive and reproducible shotgun proteomics approach that includes an efficient mAb depletion strategy and addresses the shortcomings of such workflows. Our methodology is potentially a valuable complement or alternative to ELISA. Additionally, it can facilitate the purification process development and the evaluation of ELISA kits upon process changes.http://www.sciencedirect.com/science/article/pii/S2949771X23000129Affinity chromatographyDownstream processingHost cell proteinsLabel freeMass spectrometryMonoclonal antibody
spellingShingle Somar Khalil
Adeline Wychowski
Cyrille Chéry
Annick Gervais
Label-free shotgun proteomics: Exploiting a reliable and sensitive method to monitor residual host-cell proteins in monoclonal antibody products
Journal of Pharmaceutical and Biomedical Analysis Open
Affinity chromatography
Downstream processing
Host cell proteins
Label free
Mass spectrometry
Monoclonal antibody
title Label-free shotgun proteomics: Exploiting a reliable and sensitive method to monitor residual host-cell proteins in monoclonal antibody products
title_full Label-free shotgun proteomics: Exploiting a reliable and sensitive method to monitor residual host-cell proteins in monoclonal antibody products
title_fullStr Label-free shotgun proteomics: Exploiting a reliable and sensitive method to monitor residual host-cell proteins in monoclonal antibody products
title_full_unstemmed Label-free shotgun proteomics: Exploiting a reliable and sensitive method to monitor residual host-cell proteins in monoclonal antibody products
title_short Label-free shotgun proteomics: Exploiting a reliable and sensitive method to monitor residual host-cell proteins in monoclonal antibody products
title_sort label free shotgun proteomics exploiting a reliable and sensitive method to monitor residual host cell proteins in monoclonal antibody products
topic Affinity chromatography
Downstream processing
Host cell proteins
Label free
Mass spectrometry
Monoclonal antibody
url http://www.sciencedirect.com/science/article/pii/S2949771X23000129
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