Glypican-3结构、生物学功能及其肝细胞癌靶向治疗研究进展

Advances in structure, biological functions of glypican-3 and its targeted therapy for hepatocellular carcinoma

肝细胞癌(hepatocellular carcinoma, HCC)是最常见的恶性肿瘤之一,但现有治疗方法效果均不甚理想。磷脂酰肌醇蛋白聚糖-3 (glypican-3, GPC3)是肝癌诊断的特异性生物标志物,也是HCC靶向治疗的潜在靶标。近年来,针对GPC3蛋白的靶向治疗包括抗体、抗体-药物偶联物(ADC)、免疫毒素、肿瘤疫苗、靶向肽、嵌合抗原受体、基因治疗等,并且以其为靶点进行了大量药物的研发和细胞治疗研究,其中有一些已经进入了临床试验,如GPC3人源化单克隆抗体GC33、GPC3多肽疫苗、以GPC3为靶点的嵌合抗原受体修饰T细胞(CAR-T)等。可见,基于GPC3的HCC靶向治疗已经成为目前的研究热点。该文将从GPC3的分子结构、生物学功能及靶向GPC3的HCC治疗方法三个方面进行综述,以期为GPC3的功能研究与靶向HCC的治疗药物和策略研究提供思路。

Hepatocellular carcinoma(HCC) is one of the most common malignant tumors, but the effect of existing treatment methods is not satisfactory. Phosphatidylinositol proteoglycan-3(GPC3) is a specific biomarker for the diagnosis and a potential target molecule for targeted therapy of HCC. In recent years, targeted therapy for GPC3 protein, includes antibodies, antibody-drug conjugates(ADC) and immunotoxins, tumor vaccines, targeting peptides, chimeric antigen receptors, gene therapy, etc. And with it as the target, a large number of drugs have been developed, some of which have entered clinical trials, such as GPC3 humanized monoclonal antibody GC33, GPC3 polypeptide vaccine, chimeric antigen receptor modified T cells(CAR-T) targeting GPC3, etc. It can be seen that GPC3-based targeted therapy for HCC has become a research hotspot at present. In this review, we will summarize the molecular structure and the biological function of GPC3, and the treatment methods of HCC targeting GPC3.