Gene therapy of hepatoma by intratumoral injection with thymidine kinase gene and ganciclovir administration

Abstract

A retroviral expression vector carrying herpes simplex virus thymidine kinase gene (pZIPtkn) was constructed and transfected into ψ2 packaging cells (ψ2tkn). Retrovirus produced by the ψ2tkn cells was transduced into XC rat hepatoma cells (XCtkn2). The growth of XCtkn2 cells transplanted into nude mice was suppressed by ganciclovir administration. In addition, the growth of genetically unmodified XC cells which had been transplanted into nude mice was also inhibited by intratumoral injection of XCtkn2 or y2tkn cells and subsequent ganciclovir administration. However, direct intratumoral injection of the pZIPtkn-cationic liposome complexes and subsequent ganciclovir treatment did not inhibit the in vivo growth of genetically unmodified XC hepatoma cells. These suggest that the intratumoral injection of cells carrying herpes simplex virus thymidine kinase gene followed by ganciclovir administration appears to be useful for the treatment of hepatoma.