
<ArticleTitle>Systemic <prot>IFN-beta</prot> gene therapy results in long-term survival in mice with established colorectal liver metastases.</ArticleTitle>
<AbstractText>Most patients succumbing to colorectal cancer fail with liver-predominant metastases. To make a clinical impact in this disease, a systemic or whole-liver therapy may be required, whereas most cancer gene therapy approaches are limited in their ability to treat beyond local disease. As a preclinical model for cancer gene therapy, recombinant adenovirus containing the human <prot>IFN-beta</prot> (<prot>hIFN-beta</prot>) cDNA was delivered systemically in nude mouse xenograft models of human colorectal cancer liver metastases. The vector targeted hepatocytes that produced high levels of <prot>hIFN-beta</prot> in the liver, resulting in a profound apoptotic response in the tumors and significant tumor regression. <prot>hIFN-beta</prot> gene therapy not only resulted in improved survival and long-term cure in a micrometastatic model, but provided similar benefits in a clinically relevant gross disease model. A similar recombinant adenovirus containing the murine <prot>IFN-beta</prot> (<prot>mIFN-beta</prot>) cDNA also resulted in a therapeutic response and improved survival in syngeneic mouse models of colorectal cancer liver metastases. Depletion studies demonstrate a contribution of natural killer cells to this therapeutic response. The toxicity of an adenoviral vector expressing murine <prot>IFN-beta</prot> in a syngeneic model is also presented. These encouraging results warrant further investigation of the use of cancer gene therapy for targeting metastatic disease.</AbstractText>
