Issue 4, 2021

Aggregation of protein therapeutics enhances their immunogenicity: causes and mitigation strategies

Abstract

Protein aggregation in biotherapeutics has been identified to increase immunogenicity, leading to immune-mediated adverse effects, such as severe allergic responses including anaphylaxis. The induction of anti-drug antibodies (ADAs) moreover enhances drug clearance rates, and can directly block therapeutic function. In this review, identified immune activation mechanisms triggered by protein aggregates are discussed, as well as physicochemical properties of aggregates, such as size and shape, which contribute to immunogenicity. Furthermore, factors which contribute to protein stability and aggregation are considered. Lastly, with these factors in mind, we encourage an innovative and multidisciplinary approach with regard to further research in the field, with the overall aim to avoid immunogenic aggregation in future drug development.

Graphical abstract: Aggregation of protein therapeutics enhances their immunogenicity: causes and mitigation strategies

Article information

Article type
Review Article
Submitted
29 mar 2021
Accepted
04 maj 2021
First published
04 maj 2021
This article is Open Access
Creative Commons BY license

RSC Chem. Biol., 2021,2, 1004-1020

Aggregation of protein therapeutics enhances their immunogenicity: causes and mitigation strategies

M. L. E. Lundahl, S. Fogli, P. E. Colavita and E. M. Scanlan, RSC Chem. Biol., 2021, 2, 1004 DOI: 10.1039/D1CB00067E

This article is licensed under a Creative Commons Attribution 3.0 Unported Licence. You can use material from this article in other publications without requesting further permissions from the RSC, provided that the correct acknowledgement is given.

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