为肝细胞癌武装 GPC3 CAR-T 细胞：多少才足够，下一步是什么？
Armouring GPC3 CAR T cells for hepatocellular carcinoma: how much is enough and what comes next?
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
紧密连接蛋白作为治疗肝纤维化和肝细胞癌的治疗靶点
英文原题：Tight Junction Proteins as Therapeutic Targets to Treat Liver Fibrosis and Hepatocellular Carcinoma.
查看英文原题
Tight Junction Proteins as Therapeutic Targets to Treat Liver Fibrosis and Hepatocellular Carcinoma.
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中文摘要
在过去十年中，暴露于肝细胞或癌细胞表面的紧密连接蛋白已被发现是肝病生物学的介质：Claudin-1和Occludin是丙型肝炎病毒进入的宿主因子，而Claudin-1已被确定为肝纤维化和肝细胞癌（HCC）的驱动因素。此外，Claudins已成为肝病和HCC的治疗靶点。CLDN1表达在肝纤维化和HCC中上调。靶向Claudin-1的单克隆抗体（mAbs）已完成用于治疗肝纤维化和HCC的临床前概念验证研究，目前正处于晚期肝纤维化的临床开发阶段。Claudin-6过表达与HCC侵袭性表型和治疗耐药相关。Claudin-6 mAbs或嵌合抗原受体-T细胞疗法目前正在针对Claudin-6过表达肿瘤进行临床研究。总之，靶向Claudin蛋白为治疗晚期肝纤维化和HCC患者提供了新的临床机会。
展开英文摘要原文
In the last decade tight junction proteins exposed at the surface of liver or cancer cells have been uncovered as mediators of liver disease biology: Claudin-1 and Occludin are host factors for hepatitis C virus entry and Claudin-1 has been identified as a driver for liver fibrosis and hepatocellular carcinoma (HCC).
Moreover, Claudins have emerged as therapeutic targets for liver disease and HCC. CLDN1 expression is upregulated in liver fibrosis and HCC. Monoclonal antibodies (mAbs) targeting Claudin-1 have completed preclinical proof-of-concept studies for treatment of liver fibrosis and HCC and are currently in clinical development for advanced liver fibrosis.
Claudin-6 overexpression is associated with an HCC aggressive phenotype and treatment resistance. Claudin-6 mAbs or chimeric antigen receptor-T cells therapies are currently being clinically investigated for Claudin-6 overexpressing tumors.
In conclusion, targeting Claudin proteins offers a novel clinical opportunity for the treatment of patients with advanced liver fibrosis and HCC.
论文信息
- 作者
- Saviano A、Roehlen N、Baumert TF
- 单位
- Inserm, U1110, Institute of Translational Medicine and Liver Disease, Strasbourg, France.France
- 文献类型
- 综述 · 非美国政府资助研究
- 期刊
- Seminars in liver disease2024 May
- 原文标识
- PubMed 38648796 · DOI 10.1055/s-0044-1785646