Inflammation and Immunology Research Unit, Pfizer, Inc. , Cambridge, MA, USA.
J Exp Med. 2024 Nov 4;221(11). doi: 10.1084/jem.20240806. Epub 2024 Sep 19.
Dysregulated signaling from TNF and TNFR proteins is implicated in several immune-mediated inflammatory diseases (IMIDs). This review centers around seven IMIDs (rheumatoid arthritis, systemic lupus erythematosus, Crohn's disease, ulcerative colitis, psoriasis, atopic dermatitis, and asthma) with substantial unmet medical needs and sheds light on the signaling mechanisms, disease relevance, and evolving drug development activities for five TNF/TNFR signaling axes that garner substantial drug development interest in these focus conditions. The review also explores the current landscape of therapeutics, emphasizing the limitations of the approved biologics, and the opportunities presented by small-molecule inhibitors and combination antagonists of TNF/TNFR signaling.
TNF 和 TNFR 蛋白的信号失调与几种免疫介导的炎症性疾病（IMIDs）有关。这篇综述集中在七种具有重大未满足医疗需求的 IMIDs（类风湿性关节炎、系统性红斑狼疮、克罗恩病、溃疡性结肠炎、银屑病、特应性皮炎和哮喘）上，揭示了五个 TNF/TNFR 信号轴的信号机制、疾病相关性和不断发展的药物开发活动，这些活动在这些重点疾病中引起了广泛的药物开发兴趣。该综述还探讨了治疗学的现状，强调了已批准的生物制剂的局限性，以及 TNF/TNFR 信号小分子抑制剂和联合拮抗剂所带来的机遇。
