利用目标细胞因子TNF超家族的共刺激受体进行癌症免疫治疗。
Targeting Co-Stimulatory Receptors of the TNF Superfamily for Cancer Immunotherapy.
发表日期：2023 Jan
作者：
Dafne Müller
来源：
BIODRUGS
摘要：
免疫检查点抑制剂的临床批准是癌症免疫治疗领域的一个重要进展。然而，受益者的比例仍然有限，而且现在越来越明显，需要组合疗法进一步增强治疗效果。利用“踩油门”而非“刹车”来定位免疫调节网络的策略潜力正在得到认可并受到深入研究。因此，在免疫检查点抑制剂之外，肿瘤坏死因子超家族的共刺激受体激动剂（TNF-SF）作为扩展免疫调节工具箱的有希望的选择正在崛起。本文综述了重组抗体和配体类4-1BB、OX40和GITR的不同类别的激动剂的发展情况，并针对TNFR-SF的结构和机理特点讨论。提供了当前格式、趋势和临床研究的概述。© 2022. 作者。
The clinical approval of immune checkpoint inhibitors is an important advancement in the field of cancer immunotherapy. However, the percentage of beneficiaries is still limited and it is becoming clear that combination therapies are required to further enhance the treatment efficacy. The potential of strategies targeting the immunoregulatory network by "hitting the gas pedal" as opposed to "blocking the brakes" is being recognized and intensively investigated. Hence, next to immune checkpoint inhibitors, agonists of co-stimulatory receptors of the tumor necrosis factor superfamily (TNF-SF) are emerging as promising options to expand the immunomodulatory toolbox. In this review the development of different categories of recombinant antibody and ligand-based agonists of 4-1BB, OX40, and GITR is summarized and discussed in the context of the challenges presented by the structural and mechanistical features of the TNFR-SF. An overview of current formats, trends, and clinical studies is provided.© 2022. The Author(s).