Center for Autoimmunity and Inflammation, La Jolla Institute for Immunology, La Jolla, CA, USA.
Inhibrx, La Jolla, CA, USA.
Nat Rev Drug Discov. 2024 Dec;23(12):939-961. doi: 10.1038/s41573-024-01053-9. Epub 2024 Oct 24.
The first anti-tumour necrosis factor (TNF) monoclonal antibody, infliximab (Remicade), celebrated its 25th anniversary of FDA approval in 2023. Inhibitors of TNF have since proved clinically efficacious at reducing inflammation associated with several autoimmune diseases, including rheumatoid arthritis, psoriasis and Crohn's disease. The success of TNF inhibitors raised unrealistic expectations for targeting other members of the TNF superfamily (TNFSF) of ligands and their receptors, with difficulties in part related to their more limited, variable expression and potential redundancy. However, there has been a resurgence of interest and investment, with many of these cytokines or their cognate receptors now under clinical investigation as targets for modulation of autoimmune and inflammatory diseases, as well as cancer. This Review assesses TNFSF-targeted biologics currently in clinical development for immune system-related diseases, highlighting ongoing challenges and future directions.
2023 年，首款抗肿瘤坏死因子（TNF）单克隆抗体英夫利昔单抗（Remicade）迎来了美国食品药品监督管理局（FDA）批准上市 25 周年。自此，TNF 抑制剂已被证明在减轻与多种自身免疫性疾病（包括类风湿关节炎、银屑病和克罗恩病）相关的炎症方面具有临床疗效。TNF 抑制剂的成功带来了针对 TNF 超家族（TNFSF）配体及其受体的其他成员进行靶向治疗的不切实际的期望，部分困难与它们更有限、更易变的表达和潜在的冗余性有关。然而，人们的兴趣和投资再次高涨，这些细胞因子或其同源受体中有许多现已作为调节自身免疫和炎症性疾病以及癌症的靶点进行临床研究。本综述评估了目前处于临床开发阶段的用于治疗与免疫系统相关疾病的 TNFSF 靶向生物制剂，重点介绍了当前的挑战和未来的方向。
