Gene therapy for hepatocellular carcinoma using EBV plasmid vector

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We investigated plasmid vector containing EBNA1/oriP and inserted gene of Herpes simplex virus 1-Thymidine kinase (HSV 1-Tk) into the vector. We transduced the vector into cell line of human hepatoma and Ewing's sarcoma with cationic liposome or polyamidoamine dendrimer, and suicidal effect of HSV1-TK driven by EBNA1/oriP was found to be in 3 to 10 hundreds times as strong as by control plasmid driven by general promotor under administration of gancyclovir (Y Harada, M Iwai, et al. Cancer Gene Ther 7 ; 27, 2000. H Maruyama-Tabata, et al. Gene Ther 7 ; 53, 2000).We transduced vector containing EBNA1/oriP with CEA promotor into CEA-positive cell line of cholangiocarcinoma (CCC) by polyamidoamine dendrimer and suicidal effect was found to be specific for CEA-positive CCC (S Tanaka, M Iwai et al. Cancer Gene Ther 7 ; 1241, 2000). Then, we reported that suicide gene therapy with EBNA1/oriP system was effective in vitro and in vivo, and specific effect for cancer was gained by using tumor promotor in EBNA1/oriP system. In addition we studied structure and function of gap junction in ontogenic liver to clarify mechanism of "Bystander effect" in gene therapy (M Iwai, et al. J Hepatol 32 ; 11, 2000). Judging from our investigation, we should apply EBNA1/oriP system containing AFP promotor as well as gene for gap junctional protein for suicide gene therapy ofAFP-positive hepatoma cells.