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Open AccessArticle

Both IgM and IgG Antibodies against Polyethylene Glycol Can Alter the Biological Activity of Methoxy Polyethylene Glycol-Epoetin Beta in Mice

1
Institute of Biomedical Sciences, Academia Sinica, Taipei 11529, Taiwan
2
Taiwan International Graduate Program in Molecular Medicine, National Yang-Ming University and Academia Sinica, Taipei 11529, Taiwan
3
Department of Laboratory Medicine, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan
4
Division of Nephrology, Kaohsiung Medical University Hospital, Kaohsiung 80708, Taiwan
5
School of Chinese Medicine, China Medical University, Taichung 40447, Taiwan
6
Department of Biomedical Science and Environmental Biology, Center for Biomarkers and Biotech Drugs, Kaohsiung Medical University, Kaohsiung 80708, Taiwan
7
Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan
8
National Institute of Cancer Research, National Health Research Institutes, Tainan 70456, Taiwan
*
Authors to whom correspondence should be addressed.
Pharmaceutics 2020, 12(1), 15; https://doi.org/10.3390/pharmaceutics12010015
Received: 28 November 2019 / Revised: 15 December 2019 / Accepted: 18 December 2019 / Published: 21 December 2019
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 125I-PEG-EPO, resulting in PEG-EPO accumulation primarily in the liver and spleen. Accelerated clearance by the anti-PEG IgG antibody was mediated by the Fc portion of the antibody. Importantly, infusing higher doses of PEG-EPO could compensate for the inhibitory effects of anti-PEG antibodies, suggesting that pre-existing anti-PEG antibodies can be “dosed through.” Our study indicates that the bioactivity and therapeutic activity of PEG-EPO may be reduced in patients with elevated levels of pre-existing anti-PEG antibodies. New pegylated medicines with a single long PEG chain may also be affected in patients with high levels of anti-PEG antibodies. View Full-Text
Keywords: polyethylene glycol (PEG); anti-PEG antibodies; methoxy polyethylene glycol-epoetin beta; PEG-EPO; anemia; erythropoiesis polyethylene glycol (PEG); anti-PEG antibodies; methoxy polyethylene glycol-epoetin beta; PEG-EPO; anemia; erythropoiesis
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Chang, T.-C.; Chen, B.-M.; Lin, W.-W.; Yu, P.-H.; Chiu, Y.-W.; Chen, Y.-T.; Wu, J.-Y.; Cheng, T.-L.; Hwang, D.-Y.; Roffler, S. Both IgM and IgG Antibodies against Polyethylene Glycol Can Alter the Biological Activity of Methoxy Polyethylene Glycol-Epoetin Beta in Mice. Pharmaceutics 2020, 12, 15.

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