PURPOSE: Human adenovirus, commonly used as a vector for gene therapy, enters host cells by receptor mediated endocytosis. Since integrin av B5 of cell surface promotes endocytosis of adenovirus and subsequent disruption of endosome, we hypothesized that the level of integrin av B5 of target cells may determine the efficiency of adenovirus- mediated gene transfer and its therapeutic effects.
MATERIALS AND METHODS: We transduced lacZ gene or herpes simplex virus thymidine kinase (HSVtk) gene, using adenoviral vector, into human lung cancer cell lines (H1299, H157, and H322). Then we evaluated the relationship between the level of integrin av B5 and av 53 of target cells, and adenovirus-mediated gene transduction efficiency.
RESULTS: The trasduction efficiency, observed by X-gal stain and B-gal activity after infection of recombinant-adenovirus encoding lacZ gene, was correlated with the level of integrin av B5, assessed by Western blotting. The bystander mediated cell killing, after transduction of HSVtk gene, was also correlated with the level of integrin av B5 of cell lines.
CONCLUSION: These results suggest that quantitative measurement of the level of integrin av B5 of target cells may be a useful predictor of the efficiency and effectiveness of gene transfer by means of an adenoviral vector.
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