[Immunization with dendritic cells infected with human AFP adenovirus vector effectively elicits immunity against mouse hepatocellular carcinomas].
OBJECTIVE
To investigate the effects of dendritic cells (DCs) infected with adenovirus vector encoding xenogeneic alpha-fetoprotein (AFP) on breaking the immune tolerance and induction of immunity against hepatocellular carcinomas.


METHODS
Human and mouse alpha-fetoprotein full-length cDNA were cloned from human HepG2 and mouse Hepa 1 - 6 hepatoma cell lines, respectively, using RT-PCR, and then inserted into adenoviral shuttle vectors to construct Ad hAFP and Ad mAFP. Mice were immunized with Ad hAFP-infected DC and in vitro CTL activity against Hepa 1 - 6 cells was examined by standard (51)Cr release assay. Survival was studied of the immunized mice, with or without depletion of CD8+ or CD4+ T cells, inoculated with Hepa 1 - 6 mouse hepatoma cells.


RESULTS
The lytic activity of CTL elicited by the Ad hAFP-infected DCs were much stronger than that by Ad mAFP-infected DCs. 80% of the Ad hAFP/DCs-immunized mice of the inoculated with 5 x 10(6) Hepa 1 - 6 hepatoma cells were still alive two months after inoculation. However, the Ad mAFP/DCs-immunized mice inoculated with 1 x 10(6) Hepa 1 - 6 cells were just 20% surviving two months later. Depletion of CD8+ or CD4+ T cells abolished such an antigen-specific immunity elicited by the DCs infected with Ad hAFP.


CONCLUSIONS
Adenovirus vector-mediated xenogeneic AFP-infected DCs can effectively break the immune tolerance to hepatocellular carcinomas in an animal model and induce strong antigen-specific T cell response, which are dependent on CD8+ and CD4+ T cells.
Tan
Xiao-hua
XH
Department of Hematology, General Hospital of Beijing Military Command, Beijing 100700, China. xiaohua_t@hotmail.com
Zhu
Qing
Q
Liu
Chang
C
Liu
Xiu-li
XL
Shao
Xiao-ting
XT
Wei
Bing
B
D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D006528:Carcinoma, Hepatocellular / Q000276:immunology* / Q000473:pathology; D045744:Cell Line, Tumor; D003602:Cytotoxicity, Immunologic; D003713:Dendritic Cells / Q000276:immunology*; D005260:Female; D005822:Genetic Vectors; D006801:Humans; D007114:Immunization; D008113:Liver Neoplasms / Q000276:immunology* / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D009368:Neoplasm Transplantation; D000509:alpha-Fetoproteins / Q000276:immunology*
D000509:alpha-Fetoproteins