Gene therapy for α-fetoprotein-producing human hepatoma cells by adenovirus-mediated transfer of the herpes simplex virus thymidine kinase gene

✍ Scribed by F Kanai; Y Shiratori; Y Yoshida; H Wakimoto; H Hamada; Y Kanegae; I Saito; H Nakabayashi; T Tamaoki; T Tanaka; K Lan; N Kato; S Shiina; M Omata

• Publisher: John Wiley and Sons
• Year: 1996
• Tongue: English
• Weight: 422 KB
• Volume: 23
• Category: Article
• ISSN: 0270-9139
• DOI: 10.1002/hep.510230611

✦ Synopsis

lacZ gene driven by the b-actin -based promoter. Ex-SEE EDITORIAL ON PAGE 1696. pression of the HSVtk gene by adenovirus from AFP promoter/enhancer (AdAFPtk) induced the cells sensitive to ganciclovir (GCV) in the AFP-producing cell We have developed a recombinant replication-deline efficiently, but not in AFP-nonproducing HLF fective adenovirus containing human a-fetoprotein hepatoma cells. An in vitro bystander effect was ob- (AFP) promoter/enhancer to direct cell type -speserved when only 10% of the cells were infected with cific expression of the herpes simplex virus thymi-AdAFPtk. These findings suggest that the AFP prodine kinase (HSVtk) gene to AFP-producing hepatomoter/enhancer sequence can provide the tumorcellular carcinoma (HCC) cells. After an in vitro specific activity for the therapeutic gene expression, infection by a recombinant adenovirus carrying the and that the AdAFPtk vector induces the selective lacZ gene under the control of human AFP promoter/ growth inhibition by GCV in the adenovirus-inenhancer (AdAFPlacZ), an expression of the lacZ fected human hepatoma cells in vitro. Recombinant gene was demonstrated efficiently in AFP-producadenovirus transfer of the HSVtk gene under ing HuH-7 and HepG2 cell lines, but not in AFP-nonthe control of tumor-specific promoter followed by producing HLE and HLF cell lines, although lacZ GCV may have promise as a targeted in situ treatgene expression was demonstrated in all these cell ment for solid neoplasms. (HEPATOLOGY 1996; 23: lines when infected with adenovirus vector carrying 1359-1368.