Modulation of Hepatic Sinusoidal Cell Function by Transduction of Genes in the Liver: Gene Therapy for Hepatic Micro-Metastasis

The immune defense system in the liver is known to consist of Kupffer cells, pit cells, lymphocytes, neutrophils, and other infiltrating immune responsive cells. In the liver, Kupffer cells as well as pit cells play an important role in tumor defense and the immune surveillance system. Activation of these cells could contribute to cytotoxicity against tumor cells. In an experimental model of hepatic metastasis of colon carcinoma, biological response modifiers potentially activate these immune responsive cells and reduce hepatic metastasis of tumor cells. Since the activation of pit cells may be induced by interleukin-2 (IL-2), the local tumor surveillance system of the liver can be activated by gene transduction of IL-2 cDNA in hepatocytes using adenovirus vector. Local production of IL-2 may enhance the natural killer (NK) activity of pit cells, leading to a reduction of hepatic metastasis of colon carcinoma. The modulation of sinusoidal cells by gene transduction (gene therapy) may provide a tool to change the pathophysiology of the liver, leading to a clinical treatment for liver diseases.