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Anti-PEG antibodies: Properties, formation, testing and role in adverse immune reactions to PEGylated nano-biopharmaceuticals.
Kozma, Gergely Tibor; Shimizu, Taro; Ishida, Tatsuhiro; Szebeni, Janos.
Afiliación
  • Kozma GT; Nanomedicine Research and Education Center, Department of Translational Medicine, Semmelweis University Medical School, Budapest, Hungary; SeroScience Ltd, Budapest, Hungary.
  • Shimizu T; Department of Pharmacokinetics and Biopharmaceutics, Institute of Biomedical Sciences, Tokushima University, 1-78-1, Sho-machi, Tokushima 770-8505, Japan.
  • Ishida T; Department of Pharmacokinetics and Biopharmaceutics, Institute of Biomedical Sciences, Tokushima University, 1-78-1, Sho-machi, Tokushima 770-8505, Japan.
  • Szebeni J; Nanomedicine Research and Education Center, Department of Translational Medicine, Semmelweis University Medical School, Budapest, Hungary; SeroScience Ltd, Budapest, Hungary; Department of Nanobiotechnology and Regenerative Medicine, Faculty of Health, Miskolc University, Miskolc, Hungary. Electroni
Adv Drug Deliv Rev ; 154-155: 163-175, 2020.
Article en En | MEDLINE | ID: mdl-32745496
Conjugation of polyethylene glycols (PEGs) to proteins or drug delivery nanosystems is a widely accepted method to increase the therapeutic index of complex nano-biopharmaceuticals. Nevertheless, these drugs and agents are often immunogenic, triggering the rise of anti-drug antibodies (ADAs). Among these ADAs, anti-PEG IgG and IgM were shown to account for efficacy loss due to accelerated blood clearance of the drug (ABC phenomenon) and hypersensitivity reactions (HSRs) entailing severe allergic symptoms with occasionally fatal anaphylaxis. In addition to recapitulating the basic information on PEG and its applications, this review expands on the physicochemical factors influencing its immunogenicity, the prevalence, features, mechanism of formation and detection of anti-PEG IgG and IgM and the mechanisms by which these antibodies (Abs) induce ABC and HSRs. In particular, we highlight the in vitro, animal and human data attesting to anti-PEG Ab-induced complement (C) activation as common underlying cause of both adverse effects. A main message is that correct measurement of anti-PEG Abs and individual proneness for C activation might predict the rise of adverse immune reactions to PEGylated drugs and thereby increase their efficacy and safety.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Polietilenglicoles / Anticuerpos Tipo de estudio: Prognostic_studies / Risk_factors_studies Límite: Animals / Humans Idioma: En Revista: Adv Drug Deliv Rev Asunto de la revista: FARMACOLOGIA / TERAPIA POR MEDICAMENTOS Año: 2020 Tipo del documento: Article País de afiliación: Hungria Pais de publicación: Países Bajos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Polietilenglicoles / Anticuerpos Tipo de estudio: Prognostic_studies / Risk_factors_studies Límite: Animals / Humans Idioma: En Revista: Adv Drug Deliv Rev Asunto de la revista: FARMACOLOGIA / TERAPIA POR MEDICAMENTOS Año: 2020 Tipo del documento: Article País de afiliación: Hungria Pais de publicación: Países Bajos