Dendritic cells transduced with recombinant adenoviruses induce more efficient anti-tumor immunity than dendritic cells pulsed with peptide.
Transduction with recombinant, replication-defective adenovirus (AdV) vectors encoding a transgene is an efficient method for gene transfer into murine or human dendritic cells (DC). We previously reported that human dendritic cells transduced with recombinant adenovirus encoding the CEA gene (AdVCEA) can effectively induce antigen-specific cytotoxic T lymphocytes (CTL) in vitro. In this study, the efficacy of vaccination using AdVCEA-transduced DC was compared with peptide-pulsed DC in terms of the antigen-specific CTL activity and anti-tumor immunity to MC38/CEA2 in a murine tumor model. AdVCEA-transduced DC increased antigen-specific T-cell proliferation, augmented the number of IFN-gamma secreting T-cells and induced potent CEA-specific CTL capable of lysing target cells pulsed with CEA peptide, as well as MC38/CEA2 expressing CEA, compared to peptide-pulsed DC. Moreover, vaccination of mice with AdVCEA-transduced DC induced a potent protective and therapeutic anti-tumor immunity to MC38/CEA2 in a subcutaneous model. These data suggest that AdVCEA-transduced DC appears to be superior to peptide-pulsed DC for the induction of anti-tumor immunity against tumor cells; this occurs through augmentation of the antigen-specific CTL response and may be used as an efficient DC-based tumor vaccine applicable to clinical care.
Oh
Seong-Taek
ST
Department of Surgery, Kang-Nam St. Mary's Hospital, Catholic University of Korea, 505 Banpo-Dong, Seocho-Gu, Seoul 137-701, South Korea.
Kim
Chang-Hyun
CH
Park
Mi-Young
MY
Won
Eun-Ha
EH
Sohn
Hyun-Jung
HJ
Cho
Hyun-Il
HI
Kang
Won-Kyung
WK
Hong
Yong-Kil
YK
Kim
Tai-Gyu
TG
D000256:Adenoviridae / Q000235:genetics*; D000818:Animals; D019496:Cancer Vaccines / Q000276:immunology*; D002272:Carcinoembryonic Antigen / Q000235:genetics / Q000276:immunology*; D002478:Cells, Cultured; D003602:Cytotoxicity, Immunologic; D003713:Dendritic Cells / Q000276:immunology*; D005260:Female; D007371:Interferon-gamma / Q000096:biosynthesis; D051379:Mice; D008810:Mice, Inbred C57BL; D009369:Neoplasms / Q000276:immunology / Q000517:prevention & control*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014161:Transduction, Genetic; D022223:Vaccines, Subunit / Q000276:immunology*; D014614:Vaccines, Synthetic / Q000276:immunology
D019496:Cancer Vaccines; D002272:Carcinoembryonic Antigen; D022223:Vaccines, Subunit; D014614:Vaccines, Synthetic; D007371:Interferon-gamma