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CD28 共刺激:癌症免疫治疗中的新见解与应用

英文原题:CD28 co-stimulation: novel insights and applications in cancer immunotherapy.

查看英文原题

CD28 co-stimulation: novel insights and applications in cancer immunotherapy.

PubMed 2024/07/25(内容时间) Nat Rev Immunol Q1 · IF 47.1(JCR 2025)

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中文摘要

近年来,在理解T细胞信号传导方面取得了实质性进展,尤其是关于T细胞共受体如共刺激受体CD28的研究。这些知识对于开发创新的癌症免疫疗法起到了关键作用,包括免疫检查点阻断抗体、过继性细胞疗法、肿瘤靶向免疫刺激抗体以及调节T细胞活化的免疫刺激小分子药物。在2006年CD28超激动剂抗体临床试验失败后,靶向CD28激动作用重新成为癌症免疫治疗技术上可行且临床上具有前景的策略。在这篇综述中,我们探讨了近期对CD28分子功能及其调控的见解。我们描述了CD28如何成为当前癌症免疫疗法成功的核心,并审视了将CD28作为临床靶点研究中所产生的新问题如何增进了我们对其生物学作用的理解,并可能指导未来肿瘤学治疗策略的开发。

展开英文摘要原文

Substantial progress in understanding T cell signalling, particularly with respect to T cell co-receptors such as the co-stimulatory receptor CD28, has been made in recent years. This knowledge has been instrumental in the development of innovative immunotherapies for patients with cancer, including immune checkpoint blockade antibodies, adoptive cell therapies, tumour-targeted immunostimulatory antibodies, and immunostimulatory small-molecule drugs that regulate T cell activation.

Following the failed clinical trial of a CD28 superagonist antibody in 2006, targeted CD28 agonism has re-emerged as a technologically viable and clinically promising strategy for cancer immunotherapy. In this Review, we explore recent insights into the molecular functions and regulation of CD28.

We describe how CD28 is central to the success of current cancer immunotherapies and examine how new questions arising from studies of CD28 as a clinical target have enhanced our understanding of its biological role and may guide the development of future therapeutic strategies in oncology.

论文信息

作者
Lotze MT、Olejniczak SH、Skokos D
第一作者单位
Department of Surgery, University of Pittsburgh Hillman Cancer Center, Pittsburgh, PA, USA. lotzemt@upmc.edu.United States
通讯作者单位
Regeneron Pharmaceuticals, Tarrytown, NY, USA. dimitris.skokos@regeneron.com.United States
文献类型
综述
期刊
Nature reviews. Immunology2024 Dec
原文标识
PubMed 39054343 · DOI 10.1038/s41577-024-01061-1