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[Cancer Research 63, 847-853, February 15, 2003]
© 2003 American Association for Cancer Research

Experimental Therapeutics

Modulation of Coxsackie-Adenovirus Receptor Expression for Increased Adenoviral Transgene Expression1

Akseli Hemminki2, Anna Kanerva, Bin Liu, Minghui Wang, Ronald D. Alvarez, Gene P. Siegal and David T. Curiel

Division of Human Gene Therapy, Departments of Medicine, Pathology and Surgery, and the Gene Therapy Center [A. H., A. K., B. L., M. W., G. P. S., D. T. C.], and Departments of Biomedical Engineering [A. H.], Obstetrics and Gynecology [R. D. A.], and Pathology, Cell Biology and Surgery [G. P. S.], University of Alabama at Birmingham, Birmingham, Alabama 35294, and Cancer Gene Therapy Group, Rational Drug Development Program, Department of Oncology, Biomedicum, 00014 University of Helsinki, Finland [A. H.]

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.




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