Glypican-3靶向肝癌治疗的进展和挑战
Progress and challenges in glypican-3 targeting for hepatocellular carcinoma therapy
影响因子:4.40000
分区:医学2区 / 药学2区
发表日期:2024 Oct
作者:
Arnaud Couzinet, Toshihiro Suzuki, Tetsuya Nakatsura
摘要
Glypican-3（GPC3）是一种细胞膜锚硫酸肝素的蛋白酶蛋白酶，最近由于其在许多癌症中的表达高表达而引起了人们的注意，它是一种癌症，尤其是肝细胞癌（尤其是肝细胞癌），尤其是在成人正常组织中的较限表达。反对HCC，开发了一种从临床前研究到人类第一临床试验的疫苗。在这篇综述中，我们通过关注临床试验来介绍针对GPC3的免疫疗法的当前状态和未来前景；肽疫苗，mRNA疫苗，抗体疗法和嵌合抗原受体/T细胞受体-T细胞疗法，并讨论通过免疫疗法有效消除HCC的其他策略。GPC3是HCC免疫疗法的理想癌症抗原。在可切除的HCC中，利用生理免疫监测，免疫检查点抑制剂和GPC3目标癌症疫苗的免疫疗法似乎有望预防复发，并且可以被视为一种预防性辅助治疗。但是，与临床前研究相比，在晚期HCC中，临床试验尚未表现出足够的抗肿瘤功效。反向翻译，床到台式研究，对于确定阻碍GPC3靶标免疫疗法的因素至关重要。
Abstract
Glypican-3 (GPC3) is a cell membrane-anchored heparan sulfate proteoglycan that has recently garnered attention as a cancer antigen owing to its high expression in numerous cancers, particularly hepatocellular carcinoma (HCC), and to limited expression in adult normal tissue.Here, we propose the potential of GPC3 as a cancer antigen based on our experience with the GPC3 peptide vaccine against HCC, having developed a vaccine that progressed from preclinical studies to first-in-human clinical trials. In this review, we present a summary of the current status and future prospects of immunotherapies targeting GPC3 by focusing on clinical trials; peptide vaccines, mRNA vaccines, antibody therapy, and chimeric antigen receptor/T-cell receptor - T-cell therapy and discuss additional strategies for effectively eliminating HCC through immunotherapy.GPC3 is an ideal cancer antigen for HCC immunotherapy. In resectable HCC, immunotherapies that leverage physiological immune surveillance, immune checkpoint inhibitors, and GPC3-target cancer vaccines appear promising in preventing recurrence and could be considered as a prophylactic adjuvant therapy. However, in advanced HCC, clinical trials have not demonstrated sufficient anti-tumor efficacy, in contrast with preclinical studies. Reverse translation, bedside-to-bench research, is crucial to identify the factors that have hindered GPC3 target immunotherapies.