Targeted adenovirus-mediated transduction of human T cells in vitro and in vivo

Abstract

Clinical success in Tcell therapy has stimulated widespread efforts to increase safety and potency and to extend this technology to solid tumors. Yet progress in cell therapy remains restricted by the limited payload capacity, specificity of target cell transduction, and transgenic gene expression efficiency of applied viral vectors. This renders complex reprogramming or direct invivo applications difficult. Here, we developed a synergistic combination of trimeric adapter constructs enabling Tcell-directed transduction by the human adenoviral vector serotype C5 invitro and invivo. Rationally chosen binding partners showed receptor-specific transduction of otherwise non-susceptible human Tcells by exploiting activation stimuli. This platform remains compatible with high-capacity vectors for up to 37 kb DNA delivery, increasing payload capacity and safety because of the removal of all viral genes. Together, these findings provide a tool for targeted delivery of large payloads in Tcells as a potential avenue to overcome current limitations of Tcell therapy.