Recent Advances in Studying Interfacial Adsorption of Bioengineered Monoclonal Antibodies

Monoclonal antibodies (mAbs) are an important class of biotherapeutics; as of 2020, dozens are commercialized medicines, over a hundred are in clinical trials, and many more are in preclinical developmental stages. Therapeutic mAbs are sequence modified from the wild type IgG isoforms to varying ext...

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Autores principales: Hollowell, Peter, Li, Zongyi, Hu, Xuzhi, Ruane, Sean, Kalonia, Cavan, van der Walle, Christopher F., Lu, Jian R.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7249052/
https://www.ncbi.nlm.nih.gov/pubmed/32353995
http://dx.doi.org/10.3390/molecules25092047
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author Hollowell, Peter
Li, Zongyi
Hu, Xuzhi
Ruane, Sean
Kalonia, Cavan
van der Walle, Christopher F.
Lu, Jian R.
author_facet Hollowell, Peter
Li, Zongyi
Hu, Xuzhi
Ruane, Sean
Kalonia, Cavan
van der Walle, Christopher F.
Lu, Jian R.
author_sort Hollowell, Peter
collection PubMed
description Monoclonal antibodies (mAbs) are an important class of biotherapeutics; as of 2020, dozens are commercialized medicines, over a hundred are in clinical trials, and many more are in preclinical developmental stages. Therapeutic mAbs are sequence modified from the wild type IgG isoforms to varying extents and can have different intrinsic structural stability. For chronic treatments in particular, high concentration (≥ 100 mg/mL) aqueous formulations are often preferred for at-home administration with a syringe-based device. MAbs, like any globular protein, are amphiphilic and readily adsorb to interfaces, potentially causing structural deformation and even unfolding. Desorption of structurally perturbed mAbs is often hypothesized to promote aggregation, potentially leading to the formation of subvisible particles and visible precipitates. Since mAbs are exposed to numerous interfaces during biomanufacturing, storage and administration, many studies have examined mAb adsorption to different interfaces under various mitigation strategies. This review examines recent published literature focusing on adsorption of bioengineered mAbs under well-defined solution and surface conditions. The focus of this review is on understanding adsorption features driven by distinct antibody domains and on recent advances in establishing model interfaces suitable for high resolution surface measurements. Our summary highlights the need to further understand the relationship between mAb interfacial adsorption and desorption, solution aggregation, and product instability during fill-finish, transport, storage and administration.
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spelling pubmed-72490522020-06-10 Recent Advances in Studying Interfacial Adsorption of Bioengineered Monoclonal Antibodies Hollowell, Peter Li, Zongyi Hu, Xuzhi Ruane, Sean Kalonia, Cavan van der Walle, Christopher F. Lu, Jian R. Molecules Review Monoclonal antibodies (mAbs) are an important class of biotherapeutics; as of 2020, dozens are commercialized medicines, over a hundred are in clinical trials, and many more are in preclinical developmental stages. Therapeutic mAbs are sequence modified from the wild type IgG isoforms to varying extents and can have different intrinsic structural stability. For chronic treatments in particular, high concentration (≥ 100 mg/mL) aqueous formulations are often preferred for at-home administration with a syringe-based device. MAbs, like any globular protein, are amphiphilic and readily adsorb to interfaces, potentially causing structural deformation and even unfolding. Desorption of structurally perturbed mAbs is often hypothesized to promote aggregation, potentially leading to the formation of subvisible particles and visible precipitates. Since mAbs are exposed to numerous interfaces during biomanufacturing, storage and administration, many studies have examined mAb adsorption to different interfaces under various mitigation strategies. This review examines recent published literature focusing on adsorption of bioengineered mAbs under well-defined solution and surface conditions. The focus of this review is on understanding adsorption features driven by distinct antibody domains and on recent advances in establishing model interfaces suitable for high resolution surface measurements. Our summary highlights the need to further understand the relationship between mAb interfacial adsorption and desorption, solution aggregation, and product instability during fill-finish, transport, storage and administration. MDPI 2020-04-28 /pmc/articles/PMC7249052/ /pubmed/32353995 http://dx.doi.org/10.3390/molecules25092047 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Hollowell, Peter
Li, Zongyi
Hu, Xuzhi
Ruane, Sean
Kalonia, Cavan
van der Walle, Christopher F.
Lu, Jian R.
Recent Advances in Studying Interfacial Adsorption of Bioengineered Monoclonal Antibodies
title Recent Advances in Studying Interfacial Adsorption of Bioengineered Monoclonal Antibodies
title_full Recent Advances in Studying Interfacial Adsorption of Bioengineered Monoclonal Antibodies
title_fullStr Recent Advances in Studying Interfacial Adsorption of Bioengineered Monoclonal Antibodies
title_full_unstemmed Recent Advances in Studying Interfacial Adsorption of Bioengineered Monoclonal Antibodies
title_short Recent Advances in Studying Interfacial Adsorption of Bioengineered Monoclonal Antibodies
title_sort recent advances in studying interfacial adsorption of bioengineered monoclonal antibodies
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7249052/
https://www.ncbi.nlm.nih.gov/pubmed/32353995
http://dx.doi.org/10.3390/molecules25092047
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