Immunogenicity of Biotherapeutics: Causes and Association with Posttranslational Modifications

Today, potential immunogenicity can be better evaluated during the drug development process, and we have rational approaches to manage the clinical consequences of immunogenicity. The focus of the scientific community should be on developing sensitive diagnostics that can predict immunogenicity-medi...

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Main Authors: Anshu Kuriakose, Narendra Chirmule, Pradip Nair
Format: Article
Language:English
Published: Wiley 2016-01-01
Series:Journal of Immunology Research
Online Access:http://dx.doi.org/10.1155/2016/1298473
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author Anshu Kuriakose
Narendra Chirmule
Pradip Nair
author_facet Anshu Kuriakose
Narendra Chirmule
Pradip Nair
author_sort Anshu Kuriakose
collection DOAJ
description Today, potential immunogenicity can be better evaluated during the drug development process, and we have rational approaches to manage the clinical consequences of immunogenicity. The focus of the scientific community should be on developing sensitive diagnostics that can predict immunogenicity-mediated adverse events in the small fraction of subjects that develop clinically relevant anti-drug antibodies. Here, we discuss the causes of immunogenicity which could be product-related (inherent property of the product or might be picked up during the manufacturing process), patient-related (genetic profile or eating habits), or linked to the route of administration. We describe various posttranslational modifications (PTMs) and how they may influence immunogenicity. Over the last three decades, we have significantly improved our understanding about the types of PTMs of biotherapeutic proteins and their association with immunogenicity. It is also now clear that all PTMs do not lead to clinical immunogenicity. We also discuss the mechanisms of immunogenicity (which include T cell-dependent and T cell-independent responses) and immunological tolerance. We further elaborate on the management of immunogenicity in preclinical and clinical setting and the unique challenges raised by biosimilars, which may have different immunogenic potential from their parent biotherapeutics.
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spelling doaj-art-fa477a670a0d49609930b7943b8a8e082025-08-20T02:22:44ZengWileyJournal of Immunology Research2314-88612314-71562016-01-01201610.1155/2016/12984731298473Immunogenicity of Biotherapeutics: Causes and Association with Posttranslational ModificationsAnshu Kuriakose0Narendra Chirmule1Pradip Nair2Biocon Research Limited, Research & Development, Bangalore, Karnataka 560099, IndiaBiocon Research Limited, Research & Development, Bangalore, Karnataka 560099, IndiaBiocon Research Limited, Research & Development, Bangalore, Karnataka 560099, IndiaToday, potential immunogenicity can be better evaluated during the drug development process, and we have rational approaches to manage the clinical consequences of immunogenicity. The focus of the scientific community should be on developing sensitive diagnostics that can predict immunogenicity-mediated adverse events in the small fraction of subjects that develop clinically relevant anti-drug antibodies. Here, we discuss the causes of immunogenicity which could be product-related (inherent property of the product or might be picked up during the manufacturing process), patient-related (genetic profile or eating habits), or linked to the route of administration. We describe various posttranslational modifications (PTMs) and how they may influence immunogenicity. Over the last three decades, we have significantly improved our understanding about the types of PTMs of biotherapeutic proteins and their association with immunogenicity. It is also now clear that all PTMs do not lead to clinical immunogenicity. We also discuss the mechanisms of immunogenicity (which include T cell-dependent and T cell-independent responses) and immunological tolerance. We further elaborate on the management of immunogenicity in preclinical and clinical setting and the unique challenges raised by biosimilars, which may have different immunogenic potential from their parent biotherapeutics.http://dx.doi.org/10.1155/2016/1298473
spellingShingle Anshu Kuriakose
Narendra Chirmule
Pradip Nair
Immunogenicity of Biotherapeutics: Causes and Association with Posttranslational Modifications
Journal of Immunology Research
title Immunogenicity of Biotherapeutics: Causes and Association with Posttranslational Modifications
title_full Immunogenicity of Biotherapeutics: Causes and Association with Posttranslational Modifications
title_fullStr Immunogenicity of Biotherapeutics: Causes and Association with Posttranslational Modifications
title_full_unstemmed Immunogenicity of Biotherapeutics: Causes and Association with Posttranslational Modifications
title_short Immunogenicity of Biotherapeutics: Causes and Association with Posttranslational Modifications
title_sort immunogenicity of biotherapeutics causes and association with posttranslational modifications
url http://dx.doi.org/10.1155/2016/1298473
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