{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T21:35:24Z","timestamp":1790804124936,"version":"4.1.0"},"reference-count":37,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,2,4]],"date-time":"2022-02-04T00:00:00Z","timestamp":1643932800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>Pegylation of biopharmaceuticals is the most common strategy to increase their half-life in the blood and is associated with a reduced immunogenicity. As antigen presentation is a primary event in the activation of CD4 T-cells and initiation of Anti-Drug Antibody (ADA) response, we investigated the role of the PEG molecule on the T-cell reactivity of certolizumab pegol (CZP), a pegylated anti-TNF\u03b1 Fab. We generated T-cell lines raised against CZP and its non-pegylated form (CZNP) and demonstrated CZP primed few T-cells in comparison to CZNP. CZP-primed lines from 3 donors responded to a total of 5 epitopes, while CZNP-primed lines from 3 donors responded to a total of 7 epitopes, 4 epitopes were recognized by both CZP- and CZNP-primed lines. In line with this difference of T-cell reactivity, CZP is less internalized by the dendritic cells than CZNP. <jats:italic>In vitro<\/jats:italic> digestion assay of CZP by Cathepsin B showed a rapid removal of the PEG moiety, suggesting a limited influence of PEG on CZP proteolysis. We therefore demonstrate that pegylation diminishes antigen capture by dendritic cells, peptide presentation to T-cells and T-cell priming. This mechanism might reduce immunogenicity and contribute to the long half-life of CZP and possibly of other pegylated molecules.<\/jats:p>","DOI":"10.3389\/fimmu.2022.808606","type":"journal-article","created":{"date-parts":[[2022,2,4]],"date-time":"2022-02-04T04:57:14Z","timestamp":1643950634000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":22,"title":["Pegylation Reduces the Uptake of Certolizumab Pegol by Dendritic Cells and Epitope Presentation to T-Cells"],"prefix":"10.3389","volume":"13","author":[{"given":"Marie","family":"de Bourayne","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sylvain","family":"Meunier","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samuel","family":"Bitoun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Evelyne","family":"Correia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xavier","family":"Mariette","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Herv\u00e9","family":"Nozach","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bernard","family":"Maill\u00e8re","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,2,4]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"25","DOI":"10.1007\/s10067-016-3435-2","article-title":"Comparative Effectiveness of Biologics for the Management of Rheumatoid Arthritis: Systematic Review and Network Meta-Analysis","volume":"36","author":"Alfonso-Cristancho","year":"2017","journal-title":"Clin Rheumatol"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1586\/14750708.3.4.535","article-title":"A New Generation of High-Affinity Humanized PEGylated Fab Fragment Anti-Tumor Necrosis Factor-Alpha Monoclonal Antibodies","volume":"3","author":"Weir","year":"2006","journal-title":"Therapy"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1016\/s0169-409x(02)00026-1","article-title":"PEGylated Antibodies and Antibody Fragments for Improved Therapy: A Review","volume":"54","author":"Chapman","year":"2002","journal-title":"Adv Drug Deliv Rev"},{"key":"B4","doi-asserted-by":"publisher","first-page":"7","DOI":"10.1016\/j.jri.2016.04.284","article-title":"Certolizumab Pegol Does Not Bind the Neonatal Fc Receptor (FcRn): Consequences for FcRn-Mediated In Vitro Transcytosis and Ex Vivo Human Placental Transfer","volume":"116","author":"Porter","year":"2016","journal-title":"J Reprod Immunol"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2017-212196","article-title":"Lack of Placental Transfer of Certolizumab Pegol During Pregnancy: Results From CRIB, a Prospective, Postmarketing, Pharmacokinetic Study","volume":"77","author":"Mariette","year":"2018","journal-title":"Ann Rheum Dis"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1111\/j.1398-9995.2009.02280.x","article-title":"Anti-Infliximab IgE and Non-IgE Antibodies and Induction of Infusion-Related Severe Anaphylactic Reactions","volume":"65","author":"Vultaggio","year":"2010","journal-title":"Allergy"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1038\/nrrheum.2013.4","article-title":"Immunogenicity of Anti-TNF Biologic Therapies for Rheumatoid Arthritis","volume":"9","author":"van Schouwenburg","year":"2013","journal-title":"Nat Rev Rheumatol"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1007\/s40259-015-0134-5","article-title":"Comparative Immunogenicity of TNF Inhibitors: Impact on Clinical Efficacy and Tolerability in the Management of Autoimmune Diseases. 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