¹Department of Pediatrics, Kyoto Prefectural University of Medicine, Kamikyo, Kyoto, Japan

²Department of Microbiology, Kyoto Prefectural University of Medicine, Kamikyo, Kyoto, Japan

³Department of Third Department of Internal Medicine, Kyoto Prefectural University of Medicine, Kamikyo, Kyoto, Japan

Correspondence to: O Mazda, Department of Microbiology, Kyoto Prefectural University of Medicine, Kamikyo, Kyoto 602-8566, Japan

This study demonstrates in vivo effectiveness of a nonviral vector system, Epstein-Barr virus (EBV)-based plasmid vector coupled with polyamidoamine (PAMAM) dendrimer (EBV/polyplex), in suicide gene therapy of cancer. The EBV-based vector is a plasmid vector containing EBV nuclear antigen 1 (EBNA1) gene and oriP from EBV genome. HSV-1 tk gene was transferred into Ewing's sarcoma cell lines, A4573 and KP-EWS-YI, by using an EBV-based plasmid vector, pSES.Tk, or a conventional plasmid vector, pS.Tk. Cells transfected with pSES.Tk/dendrimer showed approximately 100 times lower ID₅₀ to ganciclovir (GCV) compared with those transfected with pS.Tk/dendrimer. Intratumoral injection of pSES.Tk/dendrimer but not pS.Tk/dendrimer drastically suppressed the growth of tumors which had generated from A4573 or Huh7 hepatocellular carcinoma (HCC) cells inoculated into severe combined immunodeficiency (SCID) mice. The treatment with pSES.Tk/dendrimer also resulted in significant prolongation of survival of the mice implanted with A4573. These results suggest that the EBV/polyplex system could be useful for in vivo suicide gene therapy of cancer. Gene Therapy (2000) 7, 53-60.

Epstein-Barr virus-based plasmid vector; episomal vector; polyamidoamine dendrimer; gene therapy; herpes simplex virus thymidine kinase; Ewing's sarcoma