Details

Autor(en) / Beteiligte

• Tada, H
• Maron, D J
• Choi, E A
• Barsoum, J
• Lei, H
• Xie, Q
• Liu, W
• Ellis, L
• Moscioni, A D
• Tazelaar, J
• Fawell, S
• Qin, X
• Propert, K J
• Davis, A
• Fraker, D L
• Wilson, J M
• Spitz, F R

Titel

Systemic IFN-beta gene therapy results in long-term survival in mice with established colorectal liver metastases

Ist Teil von

• The Journal of clinical investigation, 2001-07, Vol.108 (1), p.83-95

Ort / Verlag

United States: American Society for Clinical Investigation

Erscheinungsjahr

2001

Quelle

MEDLINE

Beschreibungen/Notizen

• 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.