Induction of sensitivity to ganciclovir in human hepatocellular carcinoma cells by adenovirus‐mediated gene transfer of herpes simplex virus thymidine kinase

We have analyzed the ability of a recombinant replication‐defective adenovirus to transfer the thymidine kinase gene of herpes simplex virus (HSV‐tk) into hepatocellular carcinoma (HCC) cells to confer sensitivity to ganciclovir. Three HCC cell lines (Hep3B, PLC/PRF/5, and HepG2) were efficiently infected in vitro by a recombinant adenovirus carrying lacZ reporter gene (Ad‐CMVlacZ). Expression of HSV‐tk in HCC cells infected with a recombinant adenovirus carrying HSV‐tk gene (AdCMVtk) induced sensitivity to ganciclovir in a dosedependent manner. A bystander killing effect was observed when 90% of uninfected tumor cells were mixed with only 10% of AdCMVtk‐infected cells. These data show that recombinant adenoviruses are efficient vectors for transduction of drug‐sensitizing genes to HCC cells in vitro . We suggest that a gene therapy approach to hepatocellular carcinoma can be established using adenoviral transfer of HSV‐tk to tumor cells and subsequent administration of ganciclovir. (H EPATOLOGY 1995; 22:118‐123.)