Inserm, Inflammation, Microbiome and Immunosurveillance, Université Paris-Saclay, Châtenay-Malabry, France.
Front Immunol. 2020 May 5;11:725. doi: 10.3389/fimmu.2020.00725. eCollection 2020.
Patients treated with bioproducts (BPs) frequently develop anti-drug antibodies (ADAs) with potential neutralizing capacities leading to loss of clinical response or potential hypersensitivity reactions. Many factors can influence BP immunogenicity and could be related to the patient, the treatment, as well as to the product itself. Among these latter factors, it is now well accepted that BP aggregation is associated with an increased potential for immunogenicity, as aggregates seem to be correlated with ADA development. Moreover, the presence of high-affinity ADAs suggests a CD4 T-cell dependent adaptive immune response and therefore a pivotal role for antigen-presenting cells (APCs), such as dendritic cells (DCs). In this review, we address the methods developed to evaluate how monoclonal antibodies could trigger the immunization process by focusing on the role of aggregated antibodies in the establishment of this response. In particular, we will present the different cell-based assays that have been used to assess the potential of antibodies and their aggregates to modulate cellular mechanisms leading to activation and the biological parameters (cellular activation markers, proliferation and secreted molecules) that can be measured to evaluate the different cell activation stages and their consequences in the propagation of the immune response. Indeed, the use of such strategies could help evaluate the risk of BP immunogenicity and their role in mitigating this risk.
接受生物制品（BP）治疗的患者经常会产生具有潜在中和能力的抗药物抗体（ADA），从而导致临床应答丧失或潜在的过敏反应。许多因素会影响 BP 的免疫原性，这些因素可能与患者、治疗以及产品本身有关。在这些因素中，现在已经公认 BP 聚集与更高的免疫原性潜力相关，因为聚集物似乎与 ADA 的发展相关。此外，高亲和力 ADA 的存在表明存在 CD4 T 细胞依赖性适应性免疫应答，因此抗原呈递细胞（APC），如树突状细胞（DC），起着关键作用。在这篇综述中，我们将讨论开发的方法，以评估单克隆抗体如何通过聚焦于聚集抗体在建立这种应答中的作用来触发免疫过程。特别地，我们将介绍已用于评估抗体及其聚集物在调节导致激活的细胞机制以及可测量的生物学参数（细胞激活标志物、增殖和分泌分子）方面的潜力的不同基于细胞的测定法，以评估不同的细胞激活阶段及其在免疫应答传播中的后果。事实上，此类策略的使用有助于评估 BP 免疫原性的风险及其在减轻这种风险方面的作用。
