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ABSTRACT Type I interferons (_α_/_β_) have significant antitumor activity although their short half-life and systemic side effects have limited their clinical utility. An alternative dosing

schedule of continuous, low-level delivery, as is achieved by gene therapy, rather than intermittent, high concentration pulsed-dosing, might avoid the toxicity of interferon while

maintaining its antitumor efficacy. We have tested a gene therapy approach in murine tumor models to treat malignancies that have shown responsiveness to interferon in clinical trials. The

tumor cell lines used were moderately sensitive to the direct effects of human interferon-_β_ (hIFN-_β_) _in vitro_. For _in vivo_ testing, systemic delivery of hIFN-_β_ was generated

following liver-targeted delivery of adeno-associated virus (AAV) vector carrying the hIFN-_β_ transgene. This prevented engraftment of subcutaneous human gliomas, and orthotopic, localized

(intrarenal) and disseminated (primarily pulmonary) human renal cell carcinomas; and caused regression of established tumors at these sites. In a syngeneic, immunocompetent model of

melanoma, AAV IFN-_β_ treatment limited subcutaneous tumor growth and prevented disseminated disease. A significant decrease in mean intratumoral vessel density was demonstrated in

hIFN-_β_-treated tumors, suggesting that in addition to a direct tumoricidal effect, the antitumor efficacy of AAV IFN-_β_ in this study was due to its ability to inhibit angiogenesis.

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support SIMILAR CONTENT BEING VIEWED BY OTHERS RESPONSE OF HUMAN MELANOMA CELL LINES TO INTERFERON-BETA GENE TRANSFER MEDIATED BY A MODIFIED ADENOVIRAL VECTOR Article Open access 21 October

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ACKNOWLEDGEMENTS This work was supported by The Alliance for Cancer Gene Therapy, as well as grants from the Assisi Foundation of Memphis 94-000, Grant #IRG-87-008-09 from the American

Cancer Society, Cancer Center Support CORE Grant, P30 CA 21765 and American Lebanese Syrian Associated Charities (ALSAC). We thank Dorothy Bush for her assistance with immunohistochemistry

and Stacey Glass for her assistance with ultrasonography. AUTHOR INFORMATION AUTHORS AND AFFILIATIONS * Department of Surgery, St Jude Children's Research Hospital, TN, USA C J Streck, 

P V Dickson, C Y C Ng, J Zhou, M M Hall & A M Davidoff * Department of Surgery, University of Tennessee College of Medicine, Memphis, TN, USA C J Streck, P V Dickson & A M Davidoff *

Department Hematology/Oncology, St Jude Children's Research Hospital, TN, USA J T Gray * Department of Hematology/Oncology, University College London, London, UK A C Nathwani Authors *

C J Streck View author publications You can also search for this author inPubMed Google Scholar * P V Dickson View author publications You can also search for this author inPubMed Google

Scholar * C Y C Ng View author publications You can also search for this author inPubMed Google Scholar * J Zhou View author publications You can also search for this author inPubMed Google

Scholar * M M Hall View author publications You can also search for this author inPubMed Google Scholar * J T Gray View author publications You can also search for this author inPubMed 

Google Scholar * A C Nathwani View author publications You can also search for this author inPubMed Google Scholar * A M Davidoff View author publications You can also search for this author

inPubMed Google Scholar CORRESPONDING AUTHOR Correspondence to A M Davidoff. RIGHTS AND PERMISSIONS Reprints and permissions ABOUT THIS ARTICLE CITE THIS ARTICLE Streck, C., Dickson, P.,

Ng, C. _et al._ Antitumor efficacy of AAV-mediated systemic delivery of interferon-_β_. _Cancer Gene Ther_ 13, 99–106 (2006). https://doi.org/10.1038/sj.cgt.7700878 Download citation *

Received: 12 January 2005 * Revised: 23 April 2005 * Accepted: 02 May 2005 * Published: 29 July 2005 * Issue Date: 01 January 2006 * DOI: https://doi.org/10.1038/sj.cgt.7700878 SHARE THIS

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Provided by the Springer Nature SharedIt content-sharing initiative KEYWORDS * interferon * angiogenesis * gene therapy * adenoassociated viral vectors