Université Paris-Saclay, Inserm, Inflammation, Microbiome and Immunosurveillance, Orsay, France.
Eur J Immunol. 2024 Feb;54(2):e2250340. doi: 10.1002/eji.202250340. Epub 2023 Dec 3.
Internalization and processing by antigen-presenting cells such as dendritic cells (DCs) are critical steps for initiating a T-cell response to therapeutic antibodies. Consequences are the production of neutralizing antidrug antibodies altering the clinical response, the presence of immune complexes, and, in some rare cases, hypersensitivity reactions. In recent years, significant progress has been made in the knowledge of cellular uptake mechanisms of antibodies in DCs. The uptake of antibodies could be directly related to their immunogenicity by regulating the quantity of materials entering the DCs in relation to antibody structure. Here, we summarize the latest insights into cellular uptake mechanisms and pathways in DCs. We highlight the approaches to study endocytosis, the impact of endocytosis routes on T-cell response, and discuss the link between how DCs internalize therapeutic antibodies and the potential mechanisms that could give rise to immunogenicity. Understanding these processes could help in developing assays to evaluate the immunogenicity potential of biotherapeutics.
抗原呈递细胞（如树突状细胞[DC]）的内化和加工是引发治疗性抗体 T 细胞反应的关键步骤。其后果包括产生中和性抗药物抗体，改变临床反应，出现免疫复合物，在某些罕见情况下出现过敏反应。近年来，人们对抗体在 DC 中的细胞摄取机制有了更深入的了解。抗体的摄取可能与其免疫原性直接相关，通过调节与抗体结构相关的进入 DC 的物质数量来实现。在这里，我们总结了 DC 中细胞摄取机制和途径的最新研究进展。我们强调了研究内吞作用的方法，内吞途径对 T 细胞反应的影响，并讨论了 DC 内化治疗性抗体的方式与可能导致免疫原性的潜在机制之间的联系。了解这些过程有助于开发评估生物疗法免疫原性潜力的检测方法。
