更昔洛韦
医学
肝细胞癌
胸苷激酶
遗传增强
重组DNA
癌症研究
自杀基因
细胞凋亡
毒性
单纯疱疹病毒
病理
内科学
病毒
免疫学
基因
生物
人巨细胞病毒
生物化学
作者
Antonio Sa Cunha,Eric Bonté,Sylvie Dubois,Yves Chrétien,T. L. Eraiser,Claude Degott,Christian Bréchot,Phuong-Lan Tran
标识
DOI:10.1016/s0168-8278(02)00111-3
摘要
The antitumor efficiency of thymidine kinase (tk) in Herpes Simplex virus-tk-based gene therapy of rat hepatocellular carcinoma (HCC) was examined by specific transcriptional targeting of tk to tumor cells by the alpha-fetoprotein (AFP) gene promoter and by multiple infusions of recombinant adenovirus Ad.AFPtk.We developed a surgical procedure that allows efficient, non-invasive delivery (during 2 months) of recombinant Ad via the intra-hepatic artery (IHA) route.Treatment of tumor-bearing rats with either three or five doses of 5x10(9)pfu Ad.AFPtk, administered every 3 days, and followed by intra-peritoneal treatment with ganciclovir (GCV), resulted in tumor growth inhibition and apoptosis, when compared to untreated tumor-bearing rats or animals treated with Ad.AFPlacZ or buffered saline. No treatment-related toxicity was noted. Antitumor efficacy, based on tumor size and number of tumors, was demonstrated in more than 50% of Ad.AFPtk+GCV-treated rats, as compared to control rats (P<0.0005).Our results demonstrate the safety and potential of multiple Ad.AFPtk administrations by the IHA route to inhibit HCC tumor growth, and support further clinical investigation of Ad.AFPtk gene therapy for treatment of multifocal tumor lesions in most primary liver cancers.
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