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ID 116267
著者
Kozma, Gergely Tibor Semmelweis University|SeroScience
Szebeni, Janos Semmelweis University|SeroScience|Miskolc University
キーワード
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)
資料タイプ
学術雑誌論文
抄録
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.
掲載誌名
Advanced Drug Delivery Reviews
ISSN
0169409X
cat書誌ID
AA10689127
AA1152215X
出版者
Elsevier
154-155
開始ページ
163
終了ページ
175
発行日
2020-08-01
権利情報
This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
EDB ID
出版社版DOI
出版社版URL
フルテキストファイル
言語
eng
著者版フラグ
出版社版
部局
薬学系