Targeting the TNF and TNFR superfamilies in autoimmune disease and cancer

Michael Croft, Shahram Salek-Ardakani, Carl F. Ware
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Abstract

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.

Abstract Image

以自身免疫性疾病和癌症中的 TNF 和 TNFR 超家族为靶点
首款抗肿瘤坏死因子(TNF)单克隆抗体英夫利昔单抗(Remicade)于 2023 年迎来了获得 FDA 批准 25 周年。从那时起,TNF 抑制剂在减轻与类风湿性关节炎、银屑病和克罗恩病等多种自身免疫性疾病相关的炎症方面被证明具有临床疗效。TNF 抑制剂的成功使人们对靶向 TNF 超家族(TNFSF)配体的其他成员及其受体产生了不切实际的期望。不过,人们对它们的兴趣和投资已重新升温,其中许多细胞因子或它们的同源受体目前正作为调节自身免疫性疾病、炎症性疾病以及癌症的靶点接受临床研究。本综述评估了目前针对免疫系统相关疾病正在进行临床开发的TNFSF靶向生物制剂,并强调了当前面临的挑战和未来的发展方向。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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