Glypican-3 (GPC3) 是一种细胞膜锚定的硫酸乙酰肝素蛋白聚糖，由于其在多种癌症（特别是肝细胞癌 (HCC)）中高表达，并且在成人正常组织中表达有限，因此最近作为癌症抗原而受到关注。 ，我们根据针对 HCC 的 GPC3 肽疫苗的经验，提出了 GPC3 作为癌症抗原的潜力，并开发了一种从临床前研究进展到首次人体临床试验的疫苗。在这篇综述中，我们以临床试验为重点，总结了针对GPC3的免疫疗法的现状和未来前景；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，利用生理免疫监视、免疫检查点抑制剂和 GPC3 靶向癌症疫苗的免疫疗法在预防复发方面似乎很有前景，可被视为预防性辅助疗法。然而，与临床前研究相比，在晚期 HCC 中，临床试验尚未证明其具有足够的抗肿瘤功效。反向翻译、床边到实验室研究对于确定阻碍 GPC3 靶点免疫疗法的因素至关重要。

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.