《生命科学》 2021, 33(1): 77-86

Glypican-3结构、生物学功能及其肝细胞癌靶向治疗研究进展

江舒雅¹ , 陈　春² , 付　静^3,* , 陈啸飞^3,4,*

¹海军军医大学基础医学院，上海 200433 ²上海交通大学附属第九人民医院药剂科，上海 201999 ³海军军医 大学附属东方肝胆外科医院，生物信号转导研究中心，上海 200438 ⁴海军军医大学药学院，上海 200433

摘　要：

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。

通讯作者：付　静 , Email:fujing-724@163.com 陈啸飞 , Email:xfchen2010@163.com

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

JIANG Shu-Ya¹ , CHEN Chun² , FU Jing^3,* , CHEN Xiao-Fei^3,4,*

¹School of Basic Medicine, Naval Medical University, Shanghai 200433, China ²Department of Pharmacy, Shanghai 9th People’s Hospital, Shanghai Jiao Tong University, Shanghai 201999, China ³Laboratory on Signal Transduction, Eastern Hepatobiliary Surgery Hospital, Naval Medical University, Shanghai 200438, China ⁴School of Pharmacy, Naval Medical University, Shanghai 200433, China

Abstract:

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.

Communication Author：FU Jing , Email:fujing-724@163.com CHEN Xiao-Fei , Email:xfchen2010@163.com