This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Choi, E. A. Articles by Spitz, F. R. Search for Related Content PubMed PubMed Citation Articles by Choi, E. A. Articles by Spitz, F. R.

Combined 5-Fluorouracil/Systemic Interferon-ß Gene Therapy Results in Long-Term Survival in Mice with Established Colorectal Liver Metastases

¹ Department of Surgery, Division of Surgical Oncology, ² Institute of Human Gene Therapy, ³ Department of Biostatistics and Epidemiology, The University of Pennsylvania Medical Center, Philadelphia, Pennsylvania; and ⁴ Biogen, Inc., Cambridge, Massachusetts

Preclinical in vitro and in vivo studies have demonstrated synergistic interactions between 5-fluorouracil (5-FU) and type I and II IFNs against human colorectal cancer cells. Despite these activities, randomized human trials have failed to identify a clinical benefit for this combination treatment. These limited clinical results may be secondary to the short half-life of recombinant IFN protein and the increased systemic toxicities of 5-FU/IFN combinations. We have previously reported an adenoviral-mediated IFN-ß gene therapy strategy, which may circumvent the pitfalls of recombinant IFN therapy. However, a dose-dependent toxicity and acute inflammatory response to systemically administered adenovirus vectors may limit the clinical application of this therapy. The combination of adenoviral-mediated IFN-ß gene therapy and 5-FU resulted in tumor regression, apoptosis, and improved survival in an established liver metastases model. These therapeutic effects were observed at a significantly lower vector dose than we had previously reported and with limited toxicity. This approach may allow for an effective clinical application of this therapy and warrants additional investigation.

This article has been cited by other articles:

				D.-M. Koh, G. Brown, Z. Meer, A. R. Norman, and J. E. Husband Diagnostic Accuracy of Rim and Segmental MRI Enhancement of Colorectal Hepatic Metastasis After Administration of Mangafodipir Trisodium Am. J. Roentgenol., February 1, 2007; 188(2): W154 - W161. [Abstract] [Full Text] [PDF]

				P. M. van Koetsveld, G. Vitale, W. W. de Herder, R. A. Feelders, K. van der Wansem, M. Waaijers, C. H. J. van Eijck, E.-J. M. Speel, E. Croze, A.-J. van der Lely, et al. Potent Inhibitory Effects of Type I Interferons on Human Adrenocortical Carcinoma Cell Growth J. Clin. Endocrinol. Metab., November 1, 2006; 91(11): 4537 - 4543. [Abstract] [Full Text] [PDF]

				C. J. Streck, P. V. Dickson, C. Y.C. Ng, J. Zhou, J. T. Gray, A. C. Nathwani, and A. M. Davidoff Adeno-Associated Virus Vector-Mediated Systemic Delivery of IFN-{beta} Combined with Low-Dose Cyclophosphamide Affects Tumor Regression in Murine Neuroblastoma Models Clin. Cancer Res., August 15, 2005; 11(16): 6020 - 6029. [Abstract] [Full Text] [PDF]