Huang H, Chen S H, Kosai K, Finegold M J, Woo S L
Department of Cell Biology, Baylor College of Medicine, Houston, TX, USA.
Gene Ther. 1996 Nov;3(11):980-7.
To explore gene therapy as a new treatment modality for hepatocellular carcinoma, a pre-clinical animal model was established by intrahepatic implantation of a mouse hepatocellular carcinoma cell line (MH134) in syngeneic recipients. The resulting hepatic tumors were treated with a recombinant adenoviral vector expressing the murine interleukin-2 (IL-2) gene, and long-term remission was achieved in 50% of the animals. The remaining animals died of malignant ascites, which also occurs in some human patients. Those animals were treated with a second dose of the recombinant adenoviral vector by direct inoculation into the peritoneal cavity, and long-term remission of the disseminated disease was achieved in 55% of the animals. Thus, a combined cure rate of greater than 75% for primary- and disseminated hepatocellular carcinoma was achieved by successive adenovirus-mediated IL-2 gene treatments. Histopathological and immunocytochemical analyses showed massive infiltration of the tumor by macrophages and T lymphocytes in IL-2 vector treated animals. The surviving animals developed systemic antitumoral cellular immunity that protected them against challenges of parental hepatoma cells implanted at distant sites. The results suggest that IL-2 gene therapy may be a strategy applicable for the treatment of both primary and metastatic hepatocellular carcinomas in man.
为了探索基因治疗作为肝细胞癌新的治疗方式，通过在同基因受体动物肝内植入小鼠肝癌细胞系（MH134）建立了一种临床前动物模型。用表达小鼠白细胞介素-2（IL-2）基因的重组腺病毒载体治疗由此产生的肝肿瘤，50%的动物实现了长期缓解。其余动物死于恶性腹水，这在一些人类患者中也会出现。通过将重组腺病毒载体直接接种到腹腔中对这些动物进行第二次治疗，55%的动物实现了播散性疾病的长期缓解。因此，通过连续的腺病毒介导的IL-2基因治疗，原发性和播散性肝细胞癌的综合治愈率超过了75%。组织病理学和免疫细胞化学分析显示，在接受IL-2载体治疗的动物中，肿瘤有大量巨噬细胞和T淋巴细胞浸润。存活的动物产生了全身性抗肿瘤细胞免疫，保护它们免受远处植入的亲代肝癌细胞的攻击。结果表明，IL-2基因治疗可能是一种适用于治疗人类原发性和转移性肝细胞癌的策略。
