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Scientific result | Health ＆ life sciences | Biotechnology
SIMoS team, in collaboration with Bicêtre Hospital, shows that certolizumab pegol, a pegylated monoclonal antibody fragment for anti-inflammatory use, is less likely to trigger an adverse immune response than the non-pegylated form, by an in vitro approach that reveals a decrease in cellular signals of activation of the immune response by certolizumab pegol. A promising result for the development of new therapeutic antibodies.
The introduction of biopharmaceuticals (BPs) or biomedicines  is a true therapeutic revolution and has already brought clear clinical benefits to patients suffering from chronic inflammatory diseases such as rheumatoid arthritis, Crohn's disease and certain cancers. However, this type of treatment is confronted with the problem of the immunogenicity of BPs, i.e., their capacity to trigger an immune response that results mainly into the production of antibodies directed against them (anti-drug antibodies), thus diminishing their effectiveness. Monoclonal antibodies  are one of the most developed classes of biomedicines for which the problem of immunogenicity remains a major obstacle to their use in the clinic.
Pegylation  of BPs is the most common strategy to increase their half-life in blood and is associated with reduced immunogenicity. In this study, researchers investigated the response of T cells to certolizumab, a monoclonal antibody fragment directed against a protein produced in excess during Crohn's disease, TNFα , in its pegylated (certolizumab pegol, CZP) or non-pegylated (CZNP) form. T cells are the lymphocytes involved in the initiation of immune responses and, in particular, the anti-drug antibodies response. These cells are stimulated by the presence of immunogenic molecules and by other cells called dendritic cells. The researchers show that pegylation reduces the uptake of certolizumab pegol by dendritic cells and its ability to stimulate T cells. Pegylation therefore decreases the activation signals that initiate the anti-drug antibodies response. Demonstrating the mechanisms leading to lower immunogenicity of pegylated certolizumab compared to its non-pegylated form should be useful and promising for the development of new therapeutic antibodies. Contact : Bernard Maillère (email@example.com) See also : Frédéric Joliot Institute for Life Sciences - Evaluation of the immunogenicity of peptide-drugs containing non-natural modifications (cea.fr)
Marie de Bourayne, Sylvain Meunier, Samuel Bitoun, Evelyne Correia, Xavier Mariette, Hervé Nozach, Bernard Maillère. Pegylation Reduces the Uptake of Certolizumab Pegol by Dendritic Cells and Epitope Presentation to T-Cells. Front. Immunol. 13:808606 (2022) https://dx.doi.org/10.3389/fimmu.2022.808606
CEA is a French government-funded technological research organisation in four main areas: low-carbon energies, defense and security, information technologies and health technologies. A prominent player in the European Research Area, it is involved in setting up collaborative projects with many partners around the world.