T细胞免疫受体单抗联合疗法于晚期肝细胞癌一线治疗中的应用与挑战：基于两项Ⅱ期临床研究结果的述评

摘要/Abstract

摘要： 肝细胞癌 (HCC) 是全球范围内最常见的原发性肝癌类型,尽管近年来在其早期诊断和治疗方面取得了较大进展,但晚期HCC患者的预后仍较差。近年来兴起的针对HCC的免疫治疗如程序性死亡受体1（PD-1）、程序性死亡配体1（PD-L1）抑制剂,虽然在临床上显示出一定疗效,但仍存在一定程度的耐药性问题。针对免疫球蛋白和ITIM结构域的T细胞免疫受体（TIGIT）的单抗,作为一种新兴的免疫检查点抑制剂,有望与PD-1、PD-L1抑制剂联合使用进一步增强抗肿瘤免疫反应。本文主要基于AdvanTIG-206和MORPHEUS-Liver这两项Ⅱ期临床试验,总结了目前TIGIT单抗联合疗法在晚期HCC患者一线治疗中的疗效和安全性,并进一步探讨了其与PD-1、PD-L1抑制剂及抗血管靶向治疗联合应用的潜力与发展过程中可能面临的挑战,以期为晚期HCC的一线疗法探寻可能的新方向。

关键词: 晚期肝细胞癌, 免疫检查点抑制剂, TIGIT单抗体, 临床研究, 联合疗法

Abstract: Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer worldwide. Despite significant progress in the early diagnosis and treatment of HCC in recent years, the prognosis for patients with advanced HCC remains poor. Emerging immunotherapies for HCC, such as programmed death 1 (PD-1)/programmed death ligand 1 (PD-L1) inhibitors, have demonstrated some clinical efficacy, but issues with resistance persist. Monoclonal antibodies targeting T cell immunoreceptor with Ig and ITIM domains (TIGIT), as a novel immune checkpoint inhibitor, have the potential to enhance anti-tumor immune responses when used in combination with PD-1/PD-L1 inhibitors. This article, based primarily on the results of the AdvanTIG-206 and MORPHEUS-Liver Phase II clinical trials, summarizes the current efficacy and safety of TIGIT monoclonal antibody combination therapy as a first-line treatment for patients with advanced HCC. Additionally, it explores the potential and possible challenges of combining TIGIT antibodies with PD-1/PD-L1 inhibitors and targeted therapies, with the aim of identifying new directions for first-line therapy in advanced HCC.

Key words: Advanced hepatocellular carcinoma, Immune checkpoint inhibitors, TIGIT monoclonal antibodies, Clinical studies, Combination therapy

江宁, 李旭初, 黄慧瑶, 孙超, 房虹, 马海兰, 贾硕鹏, 吴大维, 唐玉, 李宁. T细胞免疫受体单抗联合疗法于晚期肝细胞癌一线治疗中的应用与挑战：基于两项Ⅱ期临床研究结果的述评[J]. 肝癌电子杂志, 2024, 11(4): 6-12.

Jiang Ning, Li Xuchu, Huang Huiyao, Sun Chao, Fang Hong, Ma Hailan, Jia Shuopeng, Wu Dawei, Tang Yu, Li Ning. Combination therapy with TIGIT monoclonal antibody in the first-line treatment of advanced hepatocellular carcinoma: a commentary based on the results of two phase-Ⅱ clinical studies[J]. Electronic Journal of Liver Tumor, 2024, 11(4): 6-12.

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