(484c) Polymer-Enhanced Adenoviral Transduction and Apoptosis of CAR-Negative Bladder Cancer Cells

The application of adenoviral gene therapy for cancer is limited by immune clearance of the virus as well as poor transduction efficiency, since the Coxsackie and Adenovirus Receptor (CAR) receptor used for viral entry serves physiologically functions in adhesion and is frequently decreased among cancer cells. Cationic polymers have been used to enhance adenoviral gene delivery, but novel polymers with low toxicity are needed to realize this approach. Parallel screening of a recently generated a library of polymers polymers led to the identification of several candidates that resulted in high levels of transgene expression and low cytotoxicity. In this study, we evaluated a novel cationic polymer from this library, EGDE-3,3', for its potential to increase adenoviral transduction of the CAR-negative bladder cancer cell line TCCSUP. The amount of adenovirus required to transduce 50-60% of the cells was reduced 100-fold when Ad.GFP was pre-incubated with the EGDE-3,3'polymer. Polyethyleneimine (pEI) also increased infectivity, but transgene expression was consistently higher with EGDE-3,3'. Pre-incubation of an adenovirus expressing a GFP-TRAIL fusion protein also significantly enhanced the amount of cell death due to the apoptotic activity of the cytokine. Thus, our results indicate that novel biocompatible polymers may be useful in improving the delivery of adenoviral gene therapy to cancer cells with reduced CAR expression profiles.