Nature Reviews Drug Discovery ( IF 122.7 ) Pub Date : 2024-10-24 , DOI: 10.1038/s41573-024-01053-9 Michael Croft, Shahram Salek-Ardakani, Carl F. Ware
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.
中文翻译:
靶向自身免疫性疾病和癌症中的 TNF 和 TNFR 超家族
首个抗肿瘤坏死因子 (TNF) 单克隆抗体英夫利昔单抗 (Remicade) 于 2023 年庆祝其获得 FDA 批准 25 周年。此后,TNF 抑制剂已被证明在临床上有效减少与多种自身免疫性疾病相关的炎症,包括类风湿性关节炎、银屑病和克罗恩病。TNF 抑制剂的成功提高了对靶向配体 TNF 超家族 (TNFSF) 其他成员及其受体的不切实际的期望,困难部分与它们更有限、可变的表达和潜在的冗余有关。然而,人们的兴趣和投资已经复苏,其中许多细胞因子或其同源受体现在正在作为调节自身免疫和炎症性疾病以及癌症的靶标进行临床研究。本综述评估了目前正在临床开发中的免疫系统相关疾病的 TNFSF 靶向生物制剂,强调了持续的挑战和未来的方向。