The Targeted Expression of Human IL 2/IFNα2b Fused Gene in Hepatoma Cells

1999 
The study explored the use of a tumor specific AFP enhancer and a liver specific albumin promoter to achieve regulated cytokine IL 2/IFNα2b fused gene expression for treatment of hepatocellular carcinoma (HCC).The human AFP enhancer(E AFP )/albumin promoter(P ALB )were amplified from human chromosme DNA by PCR method.A recombinant retrovirus including the selectable marker neo R gene and IL 2/IFNα2b fused gene controled by the E AFP P ALB was constructed.The liver targeted expression pattern of the IL 2/IFNα2b fused gene was observed when the product was tested in culture medium of the infected cells.IL 2 activity was 850 IU/10 6 cells,IFNα activity was 320 IU/10 6 cells.The results showed that E AFP P ALB combind transcriptional regulatory sequences could control the targeted expression of cytokine genes in AFP positive human hepatoma cells,and the expression level of IL 2/IFNα2b fused gene was positively correlated to the level of AFP expression in the infected cells.The expressed IL 2/IFNα2b fused protein had functions of both IL 2 and IFNα.Therefore,this study illustrates the superiority of using transcriptionally targeted recombinant retrovirus vectors in cytokine based gene therapy.
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