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Immunogenicity Risk Assessment for Multi-specific Therapeutics

The objective of this manuscript is to provide the reader with a hypothetical case study to present an immunogenicity risk assessment for a multi-specific therapeutic as part of Investigational New Drug (IND) application. In order to provide context for the bioanalytical strategies used to support t...

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Autores principales: Kroenke, Mark A., Milton, Mark N., Kumar, Seema, Bame, Eris, White, Joleen T.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer International Publishing 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8571146/
https://www.ncbi.nlm.nih.gov/pubmed/34741215
http://dx.doi.org/10.1208/s12248-021-00642-5
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author Kroenke, Mark A.
Milton, Mark N.
Kumar, Seema
Bame, Eris
White, Joleen T.
author_facet Kroenke, Mark A.
Milton, Mark N.
Kumar, Seema
Bame, Eris
White, Joleen T.
author_sort Kroenke, Mark A.
collection PubMed
description The objective of this manuscript is to provide the reader with a hypothetical case study to present an immunogenicity risk assessment for a multi-specific therapeutic as part of Investigational New Drug (IND) application. In order to provide context for the bioanalytical strategies used to support the multi-specific therapeutic presented herein, the introduction focuses on known immunogenicity risk factors. The subsequent hypothetical case study applies these principles to a specific example HC-12, based loosely on anti-TNFα and anti-IL-17A bispecific molecules previously in development, structured as an example immunogenicity risk assessment for submission to health authorities. The risk of higher incidence and safety impact of anti-drug antibodies (ADA) due to large protein complexes is explored in the context of multi-specificity and multi-valency of the therapeutic in combination with the oligomeric forms of the targets.
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spelling pubmed-85711462021-11-08 Immunogenicity Risk Assessment for Multi-specific Therapeutics Kroenke, Mark A. Milton, Mark N. Kumar, Seema Bame, Eris White, Joleen T. AAPS J Review Article The objective of this manuscript is to provide the reader with a hypothetical case study to present an immunogenicity risk assessment for a multi-specific therapeutic as part of Investigational New Drug (IND) application. In order to provide context for the bioanalytical strategies used to support the multi-specific therapeutic presented herein, the introduction focuses on known immunogenicity risk factors. The subsequent hypothetical case study applies these principles to a specific example HC-12, based loosely on anti-TNFα and anti-IL-17A bispecific molecules previously in development, structured as an example immunogenicity risk assessment for submission to health authorities. The risk of higher incidence and safety impact of anti-drug antibodies (ADA) due to large protein complexes is explored in the context of multi-specificity and multi-valency of the therapeutic in combination with the oligomeric forms of the targets. Springer International Publishing 2021-11-05 /pmc/articles/PMC8571146/ /pubmed/34741215 http://dx.doi.org/10.1208/s12248-021-00642-5 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Review Article
Kroenke, Mark A.
Milton, Mark N.
Kumar, Seema
Bame, Eris
White, Joleen T.
Immunogenicity Risk Assessment for Multi-specific Therapeutics
title Immunogenicity Risk Assessment for Multi-specific Therapeutics
title_full Immunogenicity Risk Assessment for Multi-specific Therapeutics
title_fullStr Immunogenicity Risk Assessment for Multi-specific Therapeutics
title_full_unstemmed Immunogenicity Risk Assessment for Multi-specific Therapeutics
title_short Immunogenicity Risk Assessment for Multi-specific Therapeutics
title_sort immunogenicity risk assessment for multi-specific therapeutics
topic Review Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8571146/
https://www.ncbi.nlm.nih.gov/pubmed/34741215
http://dx.doi.org/10.1208/s12248-021-00642-5
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