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阐明细胞毒性T淋巴细胞相关抗原4(CTLA-4)在肿瘤免疫中的作用:靶向抗体疗法及临床进展综述

Elucidating CTLA-4's role in tumor immunity: a comprehensive overview of targeted antibody therapies and clinical developments.

作者信息

Fu Juan, Mao Lin, Jiao Yu, Mei Desheng, Chen Yadong

机构信息

Suzhou Guo Kuang Pharmaceutical Technology Co, Sichuan, China.

College of Science, China Pharmaceutical University, Nanjing, China.

出版信息

Mol Divers. 2024 Jul 10. doi: 10.1007/s11030-024-10917-6.

Abstract

Cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) emerges as a key single-chain transmembrane glycoprotein predominantly expressed in effector T cells and regulatory T cells. It plays a crucial role in tumor immunity by modulating T cell responses. Specifically, CTLA-4 dampens T cell activation and proliferation while bolstering the survival of regulatory T cell through its competitive interaction with B7 family molecules, thereby aiding tumor cells in eluding immune detection. Given CTLA-4's significant influence on tumor immune dynamics, an array of anti-CTLA-4 antibody therapeutics have been clinically developed to combat various malignancies, including melanoma, renal cell carcinoma, colorectal carcinoma, hepatocellular carcinoma, non-small cell lung carcinoma, and pleural mesothelioma, demonstrating notable clinical therapeutic effects. This paper aims to delve into CTLA-4's integral role in tumor immunity and to encapsulate the latest advancements in the clinical research of anti-CTLA-4 antibody.

摘要

细胞毒性T淋巴细胞相关抗原4(CTLA-4)是一种关键的单链跨膜糖蛋白,主要在效应T细胞和调节性T细胞中表达。它通过调节T细胞反应在肿瘤免疫中发挥关键作用。具体而言,CTLA-4通过与B7家族分子的竞争性相互作用抑制T细胞活化和增殖,同时增强调节性T细胞的存活,从而帮助肿瘤细胞逃避免疫检测。鉴于CTLA-4对肿瘤免疫动态的重大影响,一系列抗CTLA-4抗体疗法已在临床上开发用于对抗各种恶性肿瘤,包括黑色素瘤、肾细胞癌、结直肠癌、肝细胞癌、非小细胞肺癌和胸膜间皮瘤,显示出显著的临床治疗效果。本文旨在深入探讨CTLA-4在肿瘤免疫中的重要作用,并总结抗CTLA-4抗体临床研究的最新进展。

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