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皮肤 T 细胞淋巴瘤中基于 CCR4 治疗的现状叙述性综述:聚焦 Mogamulizumab 与未来治疗

英文原题:A Narrative Review of the State of the Art of CCR4-Based Therapies in Cutaneous T-Cell Lymphomas: Focus on Mogamulizumab and Future Treatments.

查看英文原题

A Narrative Review of the State of the Art of CCR4-Based Therapies in Cutaneous T-Cell Lymphomas: Focus on Mogamulizumab and Future Treatments.

PubMed 2024/04/22(内容时间) Antibodies (Basel) Q3 · IF 3.3(JCR 2025)

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中文摘要

CCR4 受体是皮肤 T 细胞淋巴瘤(CTCL)治疗的重要靶点,因为它参与削弱针对恶性 T 细胞的免疫反应,且具有特定表达模式。莫格利珠单抗等单克隆抗体可有效结合 CCR4,抑制该受体与配体相互作用,从而减少肿瘤负荷、改善患者结局,并阻碍恶性 T 细胞迁移和存活。目前正在探索将 CCR4 抗体与化疗、放疗及其他药物联合,以期产生协同作用。此外,小分子抑制剂、可与 CCR4 相互作用的既有药物以及 CAR-T 疗法也在研究中。相关挑战包括药物耐药、脱靶效应和患者筛选;正在进行的试验通过完善方案和识别生物标志物应对这些问题。尽管已有进展,多数新兴疗法仍需真实世界数据以校准预期。总之,靶向 CCR4 的疗法在 CTCL 管理中显示出前景,但仍存在挑战。持续研究旨在优化治疗、改善结局并改变 CTCL 管理方式。本综述旨在阐明其生物学依据,并介绍处于不同研发和临床评估阶段的多种药物及目前已有证据。

展开英文摘要原文

The CCR4 receptor is a pivotal target in cutaneous T-cell lymphoma (CTCL) therapy due to its role in impairing immune responses against malignant T-cells and expression profiles. Monoclonal antibodies like mogamulizumab effectively bind to CCR4, reducing tumour burden and enhancing patient outcomes by inhibiting the receptor's interaction with ligands, thereby hindering malignant T-cell migration and survival. Combining CCR4 antibodies with chemotherapy, radiation, and other drugs is being explored for synergistic effects.

Additionally, small-molecular inhibitors, old pharmacological agents interacting with CCR4, and CAR-T therapies are under investigation. Challenges include drug resistance, off-target effects, and patient selection, addressed through ongoing trials refining protocols and identifying biomarkers. Despite advancements, real-life data for most of the emerging treatments are needed to temper expectations.

In conclusion, CCR4-targeted therapies show promise for CTCL management, but challenges persist. Continued research aims to optimise treatments, enhance outcomes, and transform CTCL management. This review aims to elucidate the biological rationale and the several agents under various stages of development and clinical evaluation with the actual known data.

论文信息

作者
Zengarini C、Guglielmo A、Mussi M、Motta G、Agostinelli C、Sabattini E、Piraccini BM、Pileri A
单位
Department of Medical and Surgical Sciences (DIMEC), University of Bologna, 40138 Bologna, Italy.Italy
文献类型
综述
期刊
Antibodies (Basel, Switzerland)2024 Apr 22
原文标识
PubMed 38804300 · DOI 10.3390/antib13020032