Overcoming anti-PEG antibody mediated accelerated blood clearance of PEGylated liposomes by pre-infusion with high molecular weight free PEG.
作者： Morgan D. McSweeney , Lauren S.L. Price , Timothy Wessler , Elizabeth C. Ciociola , Leah B. Herity
DOI: 10.1016/J.JCONREL.2019.08.017
关键词:
摘要: Abstract Antibodies that specifically bind polyethylene glycol (PEG), i.e. anti-PEG antibodies (APA), are associated with reduced efficacy and increased risk of serious adverse events for several PEGylated therapeutics. Here, we explored the concept using free PEG molecules to saturate circulating APA. Surprisingly, found 40 kDa effectively restored prolonged circulation liposomes in presence high titers pre-existing APA at least 48 h mice. In contrast, lower molecular weight (≤10 kDa) failed restore beyond a few hours. These vivo results were consistent estimates from minimal physiologically based pharmacokinetic model. Importantly, infusion appeared be safe mice previously sensitized by injection liposomes, did not elicit excess production even adaptive immunity against PEG. Our support further investigation as potential method control overcome APA, restoring possibly other
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