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* Tumour Immunology Unit, Institute of Molecular Medicine, John Radcliffe Hospital, Oxford, United Kingdom; and
Department of Immunology and Molecular Pathology, Windeyer Institute, University College, London, United Kingdom
Lentiviral vectors can efficiently transduce a variety of nondividing cells, including APCs. We assessed the immunogenicity of a lentiviral vector encoding the melanoma Ag NY-ESO-1 in HLA-A2 transgenic mice. Direct i.v. injection of NY-ESO-1 lentivirus induced NY-ESO-1157–165-specific CD8+ cells, detected ex vivo with an A2/H-2Kb chimeric class I tetramer. These NY-ESO-1157–165-specific CD8+ cells could be expanded by boosting with an NY-ESO-1 vaccinia virus and could kill NY-ESO-1157–165 peptide-pulsed targets in vivo. Such direct lentiviral vector injection was similar in potency to the injection of in vitro-transduced dendritic cells (DC). In addition, human monocyte-derived DC transduced by the NY-ESO-1 lentivirus stimulated an NY-ESO-1157–165-specific specific CTL clone. These data suggest that direct lentiviral transduction of DC in vivo might provide a powerful immunotherapeutic strategy.
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