Intravenous Injection of a Lentiviral Vector Encoding NY-ESO-1 Induces an Effective CTL Response

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-1_157-165-specific CD8⁺ cells, detected ex vivo with an A2/H-2K^b chimeric class I tetramer. These NY-ESO-1_157-165-specific CD8⁺ cells could be expanded by boosting with an NY-ESO-1 vaccinia virus and could kill NY-ESO-1^157-165 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-1 _157-165-specific specific CTL clone. These data suggest that direct lentiviral transduction of DC in vivo might provide a powerful immunotherapeutic strategy.