Abstract
An important determinant of gene transfer efficacy with adenoviral vectors is expression of the primary receptor, the coxsackie-adenovirus receptor. Unfortunately, expression may often be low in advanced clinical cancers, including ovarian, colorectal, lung, prostate, and breast cancer. In this study we investigated the feasibility of increasing transgene expression by incubating ovarian cancer cells with various agents and then performing transgene expression analysis. Fluorescence-activated cell sorting and quantitative reverse transcription-PCR were subsequently performed for correlation with receptor and mRNA up-regulation. Furthermore, the results were confirmed in purified clinical ovarian cancer specimens. Possible clinical application was tested using i.p. administration in an orthotopic ovarian cancer animal model. This approach could be useful for increasing adenoviral transgene expression in the context of clinical trials.
Footnotes
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The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
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↵1 Supported by the Sigrid Juselius Foundation, the Emil Aaltonen Foundation, the Maud Kuistila Foundation, the Finnish Medical Foundation, the Damon Runyon-Walter Winchell Cancer Research Fund, and NIH Grants RO1 CA83821, P50 CA83591, P50 CA89019, RO1 HL67962, RO1 CA86881, and U19 DK57958. Virus was prepared at the UAB Vaccine and Vector Production Facility, supported by the UAB Comprehensive Cancer Center (5-P30-CA13148). Gene transfer assays were performed in part at the UAB Gene Therapy Center Correlative Laboratories.
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↵2 To whom requests for reprints should be addressed at: Cancer Gene Therapy Group, Rational Drug Development Program, Department of Oncology, P.O. Box 63, Biomedicum, 00014 Univeristy of Helsinki, Helsinki, Finland. Fax: 358-9-1912 5155; E-mail: Akseli.Femminki{at}Helsinki.Fi
- Received May 31, 2002.
- Accepted December 11, 2002.
- ©2003 American Association for Cancer Research.
Volume 63, Issue 4
