A novel attenuated replication-competent adenovirus for melanoma therapy.
作者： I Peter , C Graf , R Dummer , W Schaffner , U F Greber
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摘要: To generate a replication-competent adenovirus (Ad) with specificity for melanoma, we constructed tissue-specific promoter restricting E1A expression to melanoma cells. The combination of four copies mouse tyrosinase enhancer element (TE) fused the human (TP) yielded up 2000-fold higher luciferase reporter activity in tyrosinase-expressing cells than nonmelanoma Insertion composite TETP construct upstream gene was combined deleting as far possible intertwined endogenous Ad enhancer/promoter (EP). resulting AdDeltaEP-TETP vector, also deleted E3 region, found replicate tyrosinase-positive cells, such SK-Mel23 efficiently wild-type Ad5, but at more 50-fold reduced level tumour and primary Injection into xenotransplanted melanomas, not HeLa-derived tumours led long-lasting regression nude mice. This virus might be useful treatment accessible lesions advanced patients.
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