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Tytuł:
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Impact of anti-PEG antibody affinity on accelerated blood clearance of pegylated epoetin beta in mice.
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Autorzy:
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Chang TC; Institute of Biomedical Sciences, Academia Sinica, Taipei 11529, Taiwan.
Chen BM; Institute of Biomedical Sciences, Academia Sinica, Taipei 11529, Taiwan.
Wu JY; Institute of Biomedical Sciences, Academia Sinica, Taipei 11529, Taiwan; School of Chinese Medicine, China Medical University, Taichung 40447, Taiwan.
Cheng TL; Department of Biomedical Science and Environmental Biology, Center for Biomarkers and Biotech Drugs, Kaohsiung Medical University, Kaohsiung 80708, Taiwan; Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan.
Roffler S; Institute of Biomedical Sciences, Academia Sinica, Taipei 11529, Taiwan; Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan. Electronic address: .
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Źródło:
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Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie [Biomed Pharmacother] 2022 Feb; Vol. 146, pp. 112502. Date of Electronic Publication: 2021 Dec 07.
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Typ publikacji:
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Journal Article
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Język:
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English
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Imprint Name(s):
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Publication: Paris : Editions Scientifiques Elsevier
Original Publication: New York, N.Y. : Masson Pub. USA, Inc., c1982-
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MeSH Terms:
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Antibody Affinity/*immunology
Erythropoietin/*immunology
Erythropoietin/*pharmacokinetics
Immunoglobulin G/*immunology
Immunoglobulin M/*immunology
Polyethylene Glycols/*pharmacokinetics
Animals ; Antigen-Antibody Complex/immunology ; Cell Line ; Clustered Regularly Interspaced Short Palindromic Repeats ; Female ; Gene Editing ; Metabolic Clearance Rate ; Mice ; Mice, Inbred BALB C ; Recombinant Proteins/immunology ; Recombinant Proteins/pharmacokinetics
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Contributed Indexing:
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Keywords: Affinity; Anti-PEG antibodies; Concentration; Methoxy polyethylene glycol-epoetin beta; PEG-EPO; Polyethylene glycol (PEG)
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Substance Nomenclature:
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0 (Antigen-Antibody Complex)
0 (Immunoglobulin G)
0 (Immunoglobulin M)
0 (Recombinant Proteins)
0 (pegylated erythropoietin)
11096-26-7 (Erythropoietin)
3WJQ0SDW1A (Polyethylene Glycols)
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Entry Date(s):
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Date Created: 20211210 Date Completed: 20220316 Latest Revision: 20220316
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Update Code:
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20240105
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DOI:
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10.1016/j.biopha.2021.112502
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PMID:
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34891120
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Antibodies that bind polyethylene glycol (PEG) can be induced by pegylated biomolecules and also exist in a significant fraction of healthy individuals who have never received pegylated medicines. The binding affinity of antibodies against PEG (anti-PEG antibodies) likely varies depending on if they are induced or naturally occurring. Anti-PEG antibodies can accelerate the clearance of pegylated medicines from the circulation, resulting in loss of drug efficacy, but it is unknown how accelerated blood clearance is affected by anti-PEG antibody affinity. We identified a panel of anti-PEG IgG and IgM antibodies with binding avidities ranging over several orders of magnitude to methoxy polyethylene glycol-epoetin beta (PEG-EPO), which is used to treat patients suffering from anemia. Formation of in vitro immune complexes between PEG-EPO and anti-PEG IgG or IgM antibodies was more obvious as antibody affinity increased. Likewise, high affinity anti-PEG antibodies produced greater accelerated blood clearance of PEG-EPO as compared to low affinity antibodies. The molar ratio of anti-PEG antibody to PEG-EPO that accelerates drug clearance in mice correlates with antibody binding avidity. Our study indicates that the bioactivity of PEG-EPO may be reduced due to rapid clearance in patients with either high concentrations of low affinity or low concentrations of high affinity anti-PEG IgG and IgM antibodies.
(Copyright © 2021 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)