基于AFP靶点的肝细胞癌的免疫治疗研究  

Immunotherapy for Hepatocellular Carcinoma Based on AFP Antigen

作　　者：张洁 汤丁越 王成烨 高雅文 徐文青 刘思雅 肖啸 吴侠 ZHANG Jie;TANG Dingyue;WANG Chengye;GAO Yawen;XU Wenqing;LIU Siya;XIAO Xiao;WU Xia(School of Bioengineering,East China University of Science and Technology,Shanghai 200237,China;School of Pharmacy,East China University of Science and Technology,Shanghai 200237,China)

机构地区：[1]华东理工大学生物工程学院,上海200237 [2]华东理工大学药学院,上海200237

出　　处：《华东理工大学学报(自然科学版)》2025年第2期219-227,共9页Journal of East China University of Science and Technology

摘　　要：甲胎蛋白(AFP)在大约70%~80%的肝细胞癌患者中表达,可作为肝细胞癌免疫治疗的靶点。目前大多以AFP为靶点的肿瘤疫苗的临床实验效果欠佳,因此急需开发一种更有效的、基于AFP抗原的治疗性肿瘤疫苗。以复制缺陷型腺病毒为载体,构建了一种肝癌治疗性病毒载体Ad-hAFPm。该载体通过表达AFP/HSP70(热休克蛋白70)融合蛋白和粒细胞-巨噬细胞集落刺激因子(GM-CSF)来实现AFP抗原的特异性靶向治疗。在两种过表达人源AFP(hAFP)的细胞系皮下移植瘤模型中模拟验证了Ad-hAFPm病毒载体的治疗效果。结果表明,Ad-hAFPm病毒在两种皮下移植瘤模型中均表现出良好的肿瘤抑制效果,肿瘤内免疫细胞浸润水平显著升高,并呈现出一定的靶向性优势。Alpha-fetoprotein(AFP)is expressed in approximately 70%to 80%of hepatocellular carcinoma(HCC)patients,serving as a target for immunotherapy.However,the clinical trial results of most AFP-based tumor vaccines have been unsatisfactory,so there is an urgent need to develop a more effective therapeutic tumor vaccine based on AFP antigen.This paper constructed an immunotherapy vector,namely Ad-hAFPm,using a replication-defective adenovirus as the vector.This vector aimed to achieve specific targeting of the AFP antigen by expressing a fusion protein of AFP and heat shock protein 70(HSP70),along with granulocyte-macrophage colony-stimulating factor(GMCSF).Both HSP70 and GM-CSF served as adjuvants to enhance the immunogenicity of tumor antigens.The therapeutic efficacy of the Ad-hAFPm vector was evaluated in xenograft models of two human AFP-overexpressing cell lines,with a non-targeted vector,Ad-hNYm,employed as a control.The results demonstrated significant tumor suppression in the Ad-hAFPm treatment group across both xenograft models.Specifically,there was a notable reduction in tumor growth rate,a decrease in tumor volume at the experimental endpoint,and a decline in serum hAFP protein secretion.These observations indicated the specific cytotoxic effects of Ad-hAFPm virus against AFP-positive tumor cells.Furthermore,enhanced infiltration of immune cells,particularly CD8+T cells,was observed in the tumor tissues of the Ad-hAFPm group,suggesting that Ad-hAFPm virus could elicit an immune response against tumor cells.

关 键 词：肝细胞癌 AFP 免疫疗法 腺病毒 治疗性肿瘤疫苗 

分 类 号：R735.9[医药卫生—肿瘤]