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

The efficiency of dendritic cells (DC) as Immunotherapeutic vaccines critic ally depends on optimal delivery of target Ags. Although DC modified by sub group C type 5 recombinant adenoviruses (rAd5) provide encouraging results, their clinical application Is hampered by the need for high viral titers t o achieve sufficient gene transfer, due to the lack of the Ad5 fiber recept or. We now demonstrate that rAd5 carrying subgroup B Ad fibers are up to 10 0-fold more potent than classical rAd5 for gene transfer and expression in human DC, rAd5 with a type 35 fiber (rAd5F35) being the most efficient vect or. This improvement relates to a greater and faster virus entry and to an increased transgene expression especially following DC maturation. Furtherm ore, these new vectors possess enhanced synergistic effects with other acti vation signals to trigger DC maturation. Consequently, rAd5F35-infected DC engineered to express the gp100 melanoma-associated Ag largely exceed rAd5- infected DC in activating gp100-specific CTL. Finally, the DC infection pat tern of rAd5F35 is fully conserved when DC are in the vicinity of primary s kin-derived fibroblasts, suggesting this vector as a candidate for in vivo targeting of DC. Thus, subgroup B fiber-modified rAd5 constitute a major br eakthrough in the exploitation of ex vivo rAd-targeted DC as clinically rel evant vaccines and may also be suitable for in Ovo genetic modification of DC.