Buckner Jane H
Center for Translational Immunology, Benaroya Research Institute at Virginia Mason, Seattle, WA, USA.
Nat Rev Rheumatol. 2025 Feb;21(2):88-97. doi: 10.1038/s41584-024-01201-w. Epub 2024 Dec 16.
Antigen-specific therapies have a long history in the treatment of allergy but have not been successful in autoimmunity. However, in the past 20 years, advances in the definition of the self-antigens that promote autoimmunity and the growing understanding of the mechanisms that maintain tolerance in health but fail in autoimmunity have led to antigen-specific approaches being considered for the treatment of autoimmune diseases. The core goal of each antigen-specific treatment approach is to remove the immune response that promotes autoimmunity whilst sparing protective responses. Approaches to antigen-specific therapy range from targeted deletion of autoreactive lymphocytes to tolerization of autoreactive T cells and active inhibition of autoimmune responses. Technologies such as vaccines, nanoparticles, cell-based therapies and gene editing are being harnessed to achieve these goals. Remaining challenges include the selection of the best antigen to target, modality and timing of administration of these therapies and the disease in which the therapies are used; overcoming these challenges will be vital to move antigen-specific therapies forward. Once established, antigen-specific therapy has the potential to be applied broadly in the area of autoimmunity.
抗原特异性疗法在过敏治疗方面有着悠久的历史，但在自身免疫性疾病治疗中尚未取得成功。然而，在过去20年里，促进自身免疫的自身抗原定义方面的进展，以及对健康状态下维持免疫耐受但在自身免疫性疾病中失效的机制的日益了解，使得抗原特异性方法被考虑用于治疗自身免疫性疾病。每种抗原特异性治疗方法的核心目标是消除促进自身免疫的免疫反应，同时保留保护性反应。抗原特异性治疗方法涵盖从靶向清除自身反应性淋巴细胞到使自身反应性T细胞耐受以及主动抑制自身免疫反应等。疫苗、纳米颗粒、细胞疗法和基因编辑等技术正被用于实现这些目标。尚存的挑战包括最佳靶向抗原的选择、这些疗法的给药方式和时机以及所应用的疾病；克服这些挑战对于推进抗原特异性疗法至关重要。一旦确立，抗原特异性疗法有可能在自身免疫领域得到广泛应用。
