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肿瘤学临床试验中的4-1BB抗体：综述

4-1BB Antibodies in Oncology Clinical Trials: A Review.

作者信息

Schwartz Robin, Vajrala Keerti, Falchook Gerald S

机构信息

Sarah Cannon Research Institute at HealthONE, Denver, CO, USA.

Kansas City University College of Osteopathic Medicine, Kansas City, MO, USA.

出版信息

J Immunother Precis Oncol. 2025 Mar 27;8(2):121-131. doi: 10.36401/JIPO-24-30. eCollection 2025 May.

DOI:10.36401/JIPO-24-30
PMID:40151672
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11936102/
Abstract

4-1BB is a transmembrane glycoprotein found on T lymphocytes, and signaling through 4-1BB activates and differentiates CD3+ and CD8+ T cells. The ability of 4-1BB to stimulate cytotoxic T-cell responses makes it a promising target for therapeutic cancer immunotherapy development. 4-1BB antibodies have shown promising antitumor activity in preclinical studies and clinical trials. Common side effects include transaminase elevation, cytopenias, fatigue, and nausea. This clinical review summarizes past and current 4-1BB antibodies in oncology clinical trials.

摘要

4-1BB是一种在T淋巴细胞上发现的跨膜糖蛋白，通过4-1BB发出的信号可激活CD3+和CD8+ T细胞并使其分化。4-1BB刺激细胞毒性T细胞反应的能力使其成为治疗性癌症免疫疗法开发的一个有前景的靶点。4-1BB抗体在临床前研究和临床试验中已显示出有前景的抗肿瘤活性。常见的副作用包括转氨酶升高、血细胞减少、疲劳和恶心。这篇临床综述总结了肿瘤学临床试验中过去和当前使用的4-1BB抗体。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e91e/11936102/0cac2d8718ab/i2590-017X-8-2-121-f01.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e91e/11936102/0cac2d8718ab/i2590-017X-8-2-121-f01.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e91e/11936102/0cac2d8718ab/i2590-017X-8-2-121-f01.jpg

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本文引用的文献

1
First-in-human, multicenter, open-label, phase I study of ATOR-1017 (evunzekibart), a 4-1BB antibody, in patients with advanced solid malignancies.ATOR-1017（evunzekibart），一种4-1BB抗体，在晚期实体恶性肿瘤患者中的首次人体、多中心、开放标签I期研究。
J Immunother Cancer. 2025 Jan 22;13(1):e010113. doi: 10.1136/jitc-2024-010113.
2
A first-in-human study of the fibroblast activation protein-targeted, 4-1BB agonist RO7122290 in patients with advanced solid tumors.一项在晚期实体瘤患者中进行的成纤维细胞激活蛋白靶向 4-1BB 激动剂 RO7122290 的首次人体研究。
Sci Transl Med. 2023 May 10;15(695):eabp9229. doi: 10.1126/scitranslmed.abp9229.
3
First-in-human study of an OX40 (ivuxolimab) and 4-1BB (utomilumab) agonistic antibody combination in patients with advanced solid tumors.
OX40（ivuxolimab）和 4-1BB（utomilumab）激动性抗体联合用于晚期实体瘤患者的首次人体研究。
J Immunother Cancer. 2022 Oct;10(10). doi: 10.1136/jitc-2022-005471.
4
Targeting 4-1BB for tumor immunotherapy from bench to bedside.靶向 4-1BB 进行肿瘤免疫治疗：从基础研究到临床应用。
Front Immunol. 2022 Sep 16;13:975926. doi: 10.3389/fimmu.2022.975926. eCollection 2022.
5
4-1BB: A promising target for cancer immunotherapy.4-1BB：癌症免疫治疗的一个有前景的靶点。
Front Oncol. 2022 Sep 14;12:968360. doi: 10.3389/fonc.2022.968360. eCollection 2022.
6
Utomilumab in Patients With Immune Checkpoint Inhibitor-Refractory Melanoma and Non-Small-Cell Lung Cancer.乌托米单抗治疗免疫检查点抑制剂治疗失败的黑色素瘤和非小细胞肺癌患者。
Front Immunol. 2022 Aug 2;13:897991. doi: 10.3389/fimmu.2022.897991. eCollection 2022.
7
Boosting Antitumor Response by Costimulatory Strategies Driven to 4-1BB and OX40 T-cell Receptors.通过驱动至4-1BB和OX40 T细胞受体的共刺激策略增强抗肿瘤反应。
Front Cell Dev Biol. 2021 Jun 30;9:692982. doi: 10.3389/fcell.2021.692982. eCollection 2021.
8
First-in-Human Study of Utomilumab, a 4-1BB/CD137 Agonist, in Combination with Rituximab in Patients with Follicular and Other CD20 Non-Hodgkin Lymphomas.utomilumab（一种 4-1BB/CD137 激动剂）联合利妥昔单抗治疗滤泡性和其他 CD20 非霍奇金淋巴瘤患者的首次人体研究。
Clin Cancer Res. 2020 Jun 1;26(11):2524-2534. doi: 10.1158/1078-0432.CCR-19-2973. Epub 2020 Mar 6.
9
CD137, an attractive candidate for the immunotherapy of lung cancer.CD137，肺癌免疫治疗的一个有吸引力的候选者。
Cancer Sci. 2020 May;111(5):1461-1467. doi: 10.1111/cas.14354. Epub 2020 Apr 3.
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A conserved intratumoral regulatory T cell signature identifies 4-1BB as a pan-cancer target.一个保守的肿瘤内调节性 T 细胞特征将 4-1BB 鉴定为一种泛癌靶点。
J Clin Invest. 2020 Mar 2;130(3):1405-1416. doi: 10.1172/JCI128672.