Highly efficient transduction of human monocyte-derived dendritic cells with subgroup B fiber-modified adenovirus vectors enhances transgene-encoded antigen presentation to cytotoxic T cells.

摘要: The efficiency of dendritic cells (DC) as immunotherapeutic vaccines critically depends on optimal delivery target Ags. Although DC modified by subgroup C type 5 recombinant adenoviruses (rAd5) provide encouraging results, their clinical application is hampered the need for high viral titers to achieve sufficient gene transfer, due lack Ad5 fiber receptor. We now demonstrate that rAd5 carrying B Ad fibers are up 100-fold more potent than classical transfer and expression in human DC, with a 35 (rAd5F35) being most efficient vector. This improvement relates greater faster virus entry an increased transgene especially following maturation. Furthermore, these new vectors possess enhanced synergistic effects other activation signals trigger Consequently, rAd5F35-infected engineered express gp100 melanoma-associated Ag largely exceed rAd5-infected activating gp100-specific CTL. Finally, infection pattern rAd5F35 fully conserved when vicinity primary skin-derived fibroblasts, suggesting this vector candidate vivo targeting DC. Thus, fiber-modified constitute major breakthrough exploitation ex rAd-targeted clinically relevant may also be suitable genetic modification