國家衛生研究院 NHRI:Item 3990099045/12412
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    题名: Both igM and igG antibodies against polyethylene glycol can alter the biological activity of methoxy polyethylene glycol-epoetin beta in mice
    作者: Chang, TC;Chen, BM;Lin, WW;Yu, PH;Chiu, YW;Chen, YT;Wu, JY;Cheng, TL;Hwang, DY;Roffler, AS
    贡献者: National Institute of Cancer Research
    摘要: 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 (125)I-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.
    日期: 2020-01
    關聯: Pharmaceutics. 2020 Jan;12(1):Article number 15.
    Link to: http://dx.doi.org/10.3390/pharmaceutics12010015
    JIF/Ranking 2023: http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=1999-4923&DestApp=IC2JCR
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:000514655800017
    Cited Times(Scopus): https://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=85077543809
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