Bristol Myers Squibb, New York, NY, USA.
Nat Rev Drug Discov. 2024 Jul;23(7):501-524. doi: 10.1038/s41573-024-00959-8. Epub 2024 Jun 5.
Despite major progress in the treatment of autoimmune diseases in the past two decades, most therapies do not cure disease and can be associated with increased risk of infection through broad suppression of the immune system. However, advances in understanding the causes of autoimmune disease and clinical data from novel therapeutic modalities such as chimeric antigen receptor T cell therapies provide evidence that it may be possible to re-establish immune homeostasis and, potentially, prolong remission or even cure autoimmune diseases. Here, we propose a 'sequential immunotherapy' framework for immune system modulation to help achieve this ambitious goal. This framework encompasses three steps: controlling inflammation; resetting the immune system through elimination of pathogenic immune memory cells; and promoting and maintaining immune homeostasis via immune regulatory agents and tissue repair. We discuss existing drugs and those in development for each of the three steps. We also highlight the importance of causal human biology in identifying and prioritizing novel immunotherapeutic strategies as well as informing their application in specific patient subsets, enabling precision medicine approaches that have the potential to transform clinical care.
尽管在过去二十年中，自身免疫性疾病的治疗取得了重大进展，但大多数疗法并不能治愈疾病，而且由于广泛抑制免疫系统，可能会增加感染的风险。然而，对自身免疫性疾病病因的认识的进步，以及嵌合抗原受体 T 细胞疗法等新型治疗模式的临床数据，为我们提供了这样一种可能，即重建免疫系统的平衡，并有可能延长缓解期，甚至治愈自身免疫性疾病。在这里，我们提出了一种“序贯免疫疗法”的框架来调节免疫系统，以帮助实现这一雄心勃勃的目标。该框架包含三个步骤：控制炎症；通过消除致病性免疫记忆细胞来重置免疫系统；通过免疫调节药物和组织修复来促进和维持免疫平衡。我们讨论了每一步骤中现有的药物和正在开发的药物。我们还强调了在确定和优先考虑新型免疫治疗策略以及为特定患者群体提供信息方面，因果生物学的重要性，这使我们能够采用精准医疗方法，有可能改变临床护理。
