Targeting metastatic disease with gene therapy

Because hepatocytes are constantly exposed to portal blood, the liver can be readily transduced with injected transgenes. Noting that this organ is also particularly prone to taking up metastatic colorectal tumor cells, Tada and colleagues have proposed to use gene therapy to render the liver a less hospitable environment for exogenous tumors. The authors show here that following intravenous injection of recombinant adenovirus, the antitumor cytokine interferon b (IFNb) is efficiently expressed in mouse hepatocytes, where it persists over a period of weeks. The expression of the cytokine not only blocks the progression of human micrometastases, but can also eliminate existing human tumors in the treated mice, a condition that better mimics the likely clinical presentation of the disease. Taking advantage of the fact that human and murine IFNb fail to recognize each others� receptors Tada et al. also show that IFNb can play two beneficial roles, causing cytotoxicity directly in the implanted tumor cells and stimulating host NK cells to attack the tumor cells and promote tumor regression.