Induction of anti-tumour immunity by dendritic cells transduced with hTERT recombinant adenovirus in mice.
Dendritic cells (DCs) transfected with recombinant, replication-defective adenovirus (Ad) vectors encoding the human telomerase reverse transcriptase (hTERT) are potent inducers of cytotoxic T lymphocytes (CTLs) and anti-tumour immunity. However, previous studies have mostly been in vitro. In this study, we sought to determine whether DCs transfected with hTERT (DC/Ad-hTERT) could elicit a potent anti-tumour immunogenic response in vivo. We found that murine DCs transfected with recombinant adenovirus encoding the hTERT gene (DC/Ad-hTERT) induced hTERT-specific CTLs in vivo effectively, compared with Ad-LacZ-transduced DC (DC/Ad-LacZ) controls. These hTERT-specific CTLs lysed various tumour cell lines in an hTERT-specific and MHC-I molecule-restricted fashion. We also found that DC/Ad-hTERT could increase antigen-specific T-cell proliferation and augment the number of IFN-gamma secreting T-cells in mice. These data suggest that the DC/Ad-hTERT vaccine may induce anti-tumour immunity against tumour cells expressing hTERT in an MHC-I molecule-restricted fashion in vivo through the augmentation of the hTERT-specific CTL response. The DC/Ad-hTERT vaccine may thus be used as an efficient DC-based tumour vaccine in clinical applications.
Chen
Ling
L
Institute of Gastroenterology of PLA, Southwest Hospital, Third Military Medical University, Chongqing 400038, China.
Tang
Xu-Dong
XD
Yu
Song-Tao
ST
Ai
Zhi-Hua
ZH
Fang
Dian-Chun
DC
Cai
Yong-Guo
YG
Luo
Yuan-Hui
YH
Liang
Guang-Ping
GP
Yang
Shi-Ming
SM
D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D019496:Cancer Vaccines / Q000276:immunology*; D003602:Cytotoxicity, Immunologic / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology* / Q000637:transplantation; D005260:Female; D005822:Genetic Vectors; D015789:HLA-A2 Antigen / Q000378:metabolism; D016130:Immunophenotyping; D007371:Interferon-gamma / Q000096:biosynthesis; D051379:Mice; D008810:Mice, Inbred C57BL; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D019098:Telomerase / Q000235:genetics / Q000276:immunology*; D014161:Transduction, Genetic; D014407:Tumor Cells, Cultured
D019496:Cancer Vaccines; D015789:HLA-A2 Antigen; D007371:Interferon-gamma; C509186:TERT protein, human; D019098:Telomerase