A genetically retargeted adenoviral vector enhances viral transduction in XXXX cell lines and primary cultured esophageal resection specimens.

@entity1 @entity9504 @entity2228 @entity5 @entity189 @entity492 @entity418 @entity369
OBJECTIVE: To evaluate if an integrin-retargeted adenoviral vector could establish a more efficient and @entity5 -specific gene transfer in @entity418 cells. SUMMARY BACKGROUND DATA: Although preclinical data indicated that adenoviral gene therapy could be a promising novel treatment modality for @entity5 , clinical results are often disappointing. An important problem is the decreased tumoral expression of the Coxsackie and adenovirus receptor (CAR), which mediates adenoviral entry. Retargeting the adenoviral vector to other cellular receptors, by inserting an @entity369 - @entity2228 - @entity492 (RGD) tripeptide in the fiber knob, might overcome this problem. METHODS: Four @entity418 cell lines and 10 fresh surgical resection specimens were cultured. All were infected with the native adenovirus (Ad) and the retargeted adenovirus (AdRGD), encoding for the reporter genes luciferase or Green Fluorescent Protein to analyze gene transfer efficiency. RESULTS: In all cell lines, an increase in viral expression per cell and an increase in the percentage of transduced cells were seen with the retargeted adenovirus. Also, in the primary cultures of @entity189 cells, a more efficient gene transfer was seen when the retargeted vector was used. This phenomenon was less pronounced in normal cells, indicating that the RGD virus transduces @entity5 cells more efficiently than normal cells. CONCLUSIONS: This study demonstrates that an RGD retargeted @entity9504 @entity1 @entity418 cells with enhanced efficiency, while in normal esophageal cells this effect is less pronounced. Therefore, this retargeted vector is expected to have a better performance in vivo, when compared with nonretargeted vectors used for @entity5 gene therapy so far.
