Targeting LAG-3: Relatlimab, Fianlimab, and ieramilimab reshape the landscape of cancer combination immunotherapy.

IF 3.2 4区医学 Q2 PATHOLOGY

Pathology, research and practice Pub Date : 2025-10-01 Epub Date: 2025-08-08 DOI:10.1016/j.prp.2025.156163

Kosar Ghasemi

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Abstract

In cancer immunotherapy, Relatlimab, Fianlimab, and Ieramilimab are monoclonal antibodies (mAbs) that target the lymphocyte-activation gene 3 (LAG-3), with U.S. Food and Drug Administration (FDA) approval. LAG-3 is one of the immune checkpoint receptors expressed on exhausted T cells within the tumor microenvironment (TME), thereby contributing to immune suppression. This phenomenon presents one of the main challenges in implementing immunotherapeutic methods in cancer. Targeting LAG-3 employing mAbs is designed to restore T-cell functionality and increase antitumor immunity. Clinical studies involving Relatlimab, Fianlimab, and Ieramilimab in combination with other immune checkpoint inhibitors (ICIs), such as anti-programmed cell death-1 (PD-1) mAbs, have demonstrated promising clinical outcomes in the treatment of melanoma. Notably, these combinations have been associated with improved progression-free survival (PFS) compared to monotherapy. This review discusses the biology of LAG-3, the pharmacological characteristics of Relatlimab, Fianlimab, and Ieramilimab, as well as their potential synergistic effects when combined with other ICIs. Moreover, it addresses resistance mechanisms, patient selection, and challenges with combination therapies in cancer.

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靶向LAG-3: relatlimumab， fianlimumab和ieramilimab重塑癌症联合免疫治疗的格局。

在癌症免疫治疗中，Relatlimab， Fianlimab和Ieramilimab是针对淋巴细胞活化基因3 （LAG-3）的单克隆抗体（mab），已获得美国食品和药物管理局（FDA）的批准。LAG-3是在肿瘤微环境（tumor microenvironment， TME）内的耗尽T细胞上表达的免疫检查点受体之一，从而参与免疫抑制。这种现象提出了在癌症中实施免疫治疗方法的主要挑战之一。利用单克隆抗体靶向LAG-3，旨在恢复t细胞功能，增强抗肿瘤免疫。涉及Relatlimab、Fianlimab和Ieramilimab与其他免疫检查点抑制剂（ICIs）（如抗程序性细胞死亡-1 （PD-1）单克隆抗体）联合的临床研究显示，在治疗黑色素瘤方面有很好的临床效果。值得注意的是，与单药治疗相比，这些联合治疗与改善无进展生存期（PFS）相关。本文综述了LAG-3的生物学特性、Relatlimab、Fianlimab和Ieramilimab的药理学特性，以及它们与其他ICIs联合使用时的潜在协同效应。此外，它还讨论了耐药机制、患者选择和癌症联合治疗的挑战。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Pathology, research and practice 医学-病理学

CiteScore

5.00

自引率

3.60%

发文量

405

审稿时长

24 days

期刊介绍： Pathology, Research and Practice provides accessible coverage of the most recent developments across the entire field of pathology: Reviews focus on recent progress in pathology, while Comments look at interesting current problems and at hypotheses for future developments in pathology. Original Papers present novel findings on all aspects of general, anatomic and molecular pathology. Rapid Communications inform readers on preliminary findings that may be relevant for further studies and need to be communicated quickly. Teaching Cases look at new aspects or special diagnostic problems of diseases and at case reports relevant for the pathologist''s practice.