Modulation of coxsackie-adenovirus receptor expression for increased adenoviral transgene expression.

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.