| Literature DB >> 11435460 |
H Tada1, D J Maron, E A Choi, J Barsoum, H Lei, Q Xie, W Liu, L Ellis, A D Moscioni, J Tazelaar, S Fawell, X Qin, K J Propert, A Davis, D L Fraker, J M Wilson, F R Spitz.
Abstract
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 IFN-beta (hIFN-beta) cDNA was delivered systemically in nude mouse xenograft models of human colorectal cancer liver metastases. The vector targeted hepatocytes that produced high levels of hIFN-beta in the liver, resulting in a profound apoptotic response in the tumors and significant tumor regression. hIFN-beta 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 IFN-beta (mIFN-beta) 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 IFN-beta in a syngeneic model is also presented. These encouraging results warrant further investigation of the use of cancer gene therapy for targeting metastatic disease.Entities:
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Year: 2001 PMID： 11435460 PMCID： PMC209332 DOI： 10.1172/JCI9841
Source DB: PubMed Journal: J Clin Invest ISSN： 0021-9738 Impact factor: 14.808