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.
Palmowski
Michael J
MJ
Tumour Immunology Unit, Institute of Molecular Medicine, John Radcliffe Hospital, Oxford, United Kingdom.
Lopes
Luciene
L
Ikeda
Yasuhiro
Y
Salio
Mariolina
M
Cerundolo
Vincenzo
V
Collins
Mary K
MK
D016915:AIDS Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D000818:Animals; D017951:Antigen Presentation / Q000235:genetics; D000938:Antigen-Presenting Cells / Q000276:immunology / Q000378:metabolism; D000951:Antigens, Neoplasm / Q000008:administration & dosage* / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism; D002460:Cell Line; D002478:Cells, Cultured; D003602:Cytotoxicity, Immunologic / Q000235:genetics*; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism / Q000637:transplantation; D005822:Genetic Vectors; D015497:HIV-1 / Q000235:genetics* / Q000276:immunology; D006801:Humans; D007275:Injections, Intravenous; D008565:Membrane Proteins / Q000008:administration & dosage* / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014161:Transduction, Genetic / Q000379:methods*
D016915:AIDS Vaccines; D000951:Antigens, Neoplasm; C104948:CTAG1B protein, human; D008565:Membrane Proteins