Centre d'Investigation Clinique, Inserm 1434, Hôpitaux Universitaires de Strasbourg, Strasbourg, France; Immunopathologie et Chimie Thérapeutique, CNRS UPR 3572, IBMC, Strasbourg, France; Service de Rhumatologie, Centre National de Référence des Maladies Autoimmunes (RESO), Hôpitaux Universitaires de Strasbourg, Strasbourg, France.
Service de Rhumatologie, Centre National de Référence des Maladies Autoimmunes (RESO), Hôpitaux Universitaires de Strasbourg, Strasbourg, France.
Drug Discov Today. 2023 Jul;28(7):103612. doi: 10.1016/j.drudis.2023.103612. Epub 2023 May 8.
Drugs of unknown mechanisms of action are no longer being developed because we have largely capitalized on our improved understanding of the immunopathogenesis of immune-mediated inflammatory diseases (IMIDs) to develop therapeutic monoclonal antibodies (mAbs) and targeted treatments. These therapies have profoundly revolutionized the care of IMIDs. However, because of the heterogeneity of IMIDs and the redundancy of the targeted molecular pathways, some patients with IMIDs might not respond to a specific targeted drug or their disease might relapse secondarily. Therefore, there is much at stake in the development of new therapeutic strategies, which include combinations of mAbs or bispecific mAbs (BsMAbs), nanobodies and nanoparticles (NPs), therapeutic vaccines, small interfering RNA (siRNA) interference, autologous hematopoietic stem cell transplantation (aHSCT), or chimeric antigen receptor (CAR)-T cells. With the broad pipeline of targeted treatments in clinical development, the therapeutic paradigm is rapidly evolving from whether new drugs will be available to the complex selection of the most adequate targeted treatment (or treatment combination) at the patient level. This paradigm change highlights the need to better characterize the heterogeneous immunological spectrum of these diseases. Only then will these novel therapeutic strategies be able to fully demonstrate their potential to treat IMIDs.
由于我们对免疫介导的炎症性疾病（IMIDs）的免疫发病机制的理解有了很大的提高，因此不再开发作用机制未知的药物，而是开发治疗性单克隆抗体（mAbs）和靶向治疗药物。这些疗法极大地改变了 IMIDs 的治疗方式。然而，由于 IMIDs 的异质性和靶向分子途径的冗余性，一些 IMIDs 患者可能对特定的靶向药物没有反应，或者他们的疾病可能会继发复发。因此，开发新的治疗策略非常重要，这些策略包括 mAbs 或双特异性 mAbs（BsMAbs）、纳米抗体和纳米颗粒（NPs）、治疗性疫苗、小干扰 RNA（siRNA）干扰、自体造血干细胞移植（aHSCT）或嵌合抗原受体（CAR）-T 细胞的组合。随着靶向治疗的广泛临床开发，治疗模式正在迅速从是否有新的药物可用转变为在患者层面上复杂地选择最合适的靶向治疗（或治疗组合）。这种范式的转变突出表明需要更好地描述这些疾病的异质免疫学谱。只有这样，这些新的治疗策略才能充分发挥其治疗 IMIDs 的潜力。
