REVIEW article
Front. Immunol.
Sec. Vaccines and Molecular Therapeutics
Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1617395
This article is part of the Research TopicAdvances in Immunogenicity Risk Assessment, Monitoring and Mitigation of BiologicsView all 8 articles
Antigen-presenting cell internalization is key for understanding and evaluating therapeutic antibodies' immunogenicity
Provisionally accepted
- Université Paris-Saclay, Inserm, Inflammation, Microbiome and Immunosurveillance, Orsay, France
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Therapeutic antibodies have revolutionized the treatment of many diseases. However, their safety and efficacy are often altered by their immunogenicity, as many patients frequently develop anti-drug antibodies. Dendritic cells (DCs) are the most potent antigen-presenting cells of the immune system. DCs initiate the immunogenic adaptive immune response by internalizing therapeutic antibodies using different pathways and receptors, leading to antigen presentation to T-cells. Recently, studies have shown that the uptake of antibodies by immune cells could contribute to their immunogenicity. This review will present in detail the different DC internalization mechanisms and then discuss the impact of therapeutic antibodies' properties and aggregation on their uptake by DCs and, therefore, their immunogenicity. We will also highlight cellular models and strategies used to evaluate antibodies' internalization. Addressing the uptake of antibodies by DCs could help to predict the risk of immunogenicity and to develop mitigation strategies.
Keywords: therapeutic antibodies, Dendritic Cells, internalization, Immunogenicity, immunoglobulin
Received: 24 Apr 2025; Accepted: 13 Aug 2025.
Copyright: © 2025 Lteif, Pallardy and TURBICA. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Isabelle TURBICA, Université Paris-Saclay, Inserm, Inflammation, Microbiome and Immunosurveillance, Orsay, France
Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.