Suicide gene therapy using
ganciclovir (GCV) with transfection of the herpes
thymidine kinase (HSVtk) gene has been studied for
cancer therapy. The present study demonstrates an efficient method of suicide gene therapy for multiple hepatic
tumors, involving repetitive transfection of the HSVtk gene driven by the
alpha-fetoprotein (AFP) promoter using hemagglutinating virus of Japan (HVJ)-
liposomes. AFP-producing cells (HUH7) and AFP-nonproducing cells (LS180) were injected subcutaneously (s.c.) to establish
tumors in nude mice. Two plasmid constructs, bacterial LacZ gene driven by the AFP promoter (AFPLacZ), and HSVtk gene driven by the AFP promoter (AFPTK1) were encapsulated into the HVJ-
liposome and used. When AFPLacZ was injected into the s.c.
tumors, expression of LacZ gene was confined to HUH7
tumors. Repeated transfection of AFPTK1 followed by GCV treatment markedly suppressed growth of HUH7
tumors, and apoptosis of HUH7 cells was recognized in the
tumor. Next, HUH7 cells were injected into the portal vein in
severe combined immunodeficiency mice to establish a hepatic
tumor model. After inoculation with the
tumor, HVJ-
liposomes containing the AFPTK1 plasmid vector were injected into the portal vein via the splenic hilum, followed by GCV treatment. This gene therapy significantly inhibited the growth of
tumors in the liver and markedly improved survival. Three
injections of the AFPTK1 plasmid vector completely inhibited
tumor growth. This procedure seems to have great potential for the treatment of multiple hepatic
tumors.