Both IgM and IgG Antibodies Against Polyethylene Glycol Can Alter the Biological Activity of Methoxy Polyethylene Glycol-Epoetin Beta in Mice.
PEG-EPO
anemia
anti-PEG antibodies
erythropoiesis
methoxy polyethylene glycol-epoetin beta
polyethylene glycol (PEG)
Journal
Pharmaceutics
ISSN: 1999-4923
Titre abrégé: Pharmaceutics
Pays: Switzerland
ID NLM: 101534003
Informations de publication
Date de publication:
21 Dec 2019
21 Dec 2019
Historique:
received:
28
11
2019
revised:
15
12
2019
accepted:
18
12
2019
entrez:
28
12
2019
pubmed:
28
12
2019
medline:
28
12
2019
Statut:
epublish
Résumé
Pre-existing antibodies that bind polyethylene glycol are present in about 40% of healthy individuals. It is currently unknown if pre-existing anti-polyethylene glycol (PEG) antibodies can alter the bioactivity of pegylated drugs with a single long PEG chain, which represents the majority of newly developed pegylated medicines. Methoxy polyethylene glycol-epoetin beta (PEG-EPO) contains a single 30 kDa PEG chain and is used to treat patients suffering from anemia. We find that the pre-existing human anti-PEG IgM and IgG antibodies from normal donors can bind to PEG-EPO. The prevalence and concentrations of anti-PEG IgM and IgG antibodies were also higher in patients that responded poorly to PEG-EPO. Monoclonal anti-PEG IgM and IgG antibodies at concentrations found in normal donors blocked the biological activity of PEG-EPO to stimulate the production of new erythrocytes in mice and accelerated the clearance of
Identifiants
pubmed: 31877813
pii: pharmaceutics12010015
doi: 10.3390/pharmaceutics12010015
pmc: PMC7022322
pii:
doi:
Types de publication
Journal Article
Langues
eng
Subventions
Organisme : Ministry of Science and Technology, Taiwan
ID : MOST 107-2320-B-001-004-MY3
Déclaration de conflit d'intérêts
The authors declare no conflict of interest. The funders had no role in the design, execution, interpretation, or writing of the study.
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