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  • Title: Anti-PEG Antibodies Inhibit the Anticoagulant Activity of PEGylated Aptamers.
    Author: Moreno A, Pitoc GA, Ganson NJ, Layzer JM, Hershfield MS, Tarantal AF, Sullenger BA.
    Journal: Cell Chem Biol; 2019 May 16; 26(5):634-644.e3. PubMed ID: 30827937.
    Abstract:
    Biopharmaceuticals have become increasingly attractive therapeutic agents and are often PEGylated to enhance their pharmacokinetics and reduce their immunogenicity. However, recent human clinical trials have demonstrated that administration of PEGylated compounds can evoke anti-PEG antibodies. Considering the ubiquity of PEG in commercial products and the presence of pre-existing anti-PEG antibodies in patients in large clinical trials evaluating a PEG-modified aptamer, we investigated how anti-PEG antibodies effect the therapeutic activities of PEGylated RNA aptamers. We demonstrate that anti-PEG antibodies can directly bind to and inhibit anticoagulant aptamer function in vitro and in vivo. Moreover, in parallel studies we detected the presence of anti-PEG antibodies in nonhuman primates after a single administration of a PEGylated aptamer. Our results suggest that anti-PEG antibodies can limit the activity of PEGylated drugs and potentially compromise the activity of otherwise effective therapeutic agents.
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