The targeted expression of interleukin-2 in human hepatocellular carcinoma cells.

To improve the safety and efficiency of human hepatocellular carcinoma (HCC) gene therapy, we explored the use of a liver-specific promoter and a tumor-specific enhancer to achieve regular IL-2 gene expression for treatment of HCC. The human alpha-fetoprotein (AFP) enhancer [E(AFP)] and the albumin promoter [P(ALB)] were amplified from human genomic DNA. We used eukaryotic expression vector pcDNA-3 for the delivery of the IL-2 gene because this plasmid is a non-transient, fast-selection expression vector. A recombinant plasmid was constructed including the selectable marker neoR gene and the human IL-2 gene derived by the E(AFP) - P(ALB). The liver-predominant expression pattern of the IL-2 gene was observed in the medium of the transfected cells. When human HCC cell lines displaying different levels of AFP and non-hepatocyte tumor cell lines were transfected with the recombinant plasmid, IL-2 was expressed highly in AFP and albumin-positive HCC cells, but low in nonhepatocyte tumor cells. Moreover, the expression level of IL-2 gene was positively proportional to the level of AFP expression in the transfected cells.