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ID 116267
Author
Kozma, Gergely Tibor Semmelweis University|SeroScience
Szebeni, Janos Semmelweis University|SeroScience|Miskolc University
Keywords
Complement
Drug targeting
Immunogenicity
Liposomes
Nanomedicines
Pharmacokinetics
Biologicals
Hypersensitivity reactions
C activation-related pseudoallergy (CARPA)
Adverse drug reactions (ADRs)
Anti-drug antibodies
Accelerated blood clearance (ABC)
Content Type
Journal Article
Description
Conjugation of polyethylene glycols (PEGs) to proteins or drug delivery nanosystems is a widely accepted method to increase the therapeutic index of complex nano-biopharmaceuticals. Nevertheless, these drugs and agents are often immunogenic, triggering the rise of anti-drug antibodies (ADAs). Among these ADAs, anti-PEG IgG and IgM were shown to account for efficacy loss due to accelerated blood clearance of the drug (ABC phenomenon) and hypersensitivity reactions (HSRs) entailing severe allergic symptoms with occasionally fatal anaphylaxis. In addition to recapitulating the basic information on PEG and its applications, this review expands on the physicochemical factors influencing its immunogenicity, the prevalence, features, mechanism of formation and detection of anti-PEG IgG and IgM and the mechanisms by which these antibodies (Abs) induce ABC and HSRs. In particular, we highlight the in vitro, animal and human data attesting to anti-PEG Ab-induced complement (C) activation as common underlying cause of both adverse effects. A main message is that correct measurement of anti-PEG Abs and individual proneness for C activation might predict the rise of adverse immune reactions to PEGylated drugs and thereby increase their efficacy and safety.
Journal Title
Advanced Drug Delivery Reviews
ISSN
0169409X
NCID
AA10689127
AA1152215X
Publisher
Elsevier
Volume
154-155
Start Page
163
End Page
175
Published Date
2020-08-01
Rights
This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
EDB ID
DOI (Published Version)
URL ( Publisher's Version )
FullText File
language
eng
TextVersion
Publisher
departments
Pharmaceutical Sciences