[Dendritic cell vaccine modified by murine mAFP gene enhances immunoprotective effect on liver carcinogenesis and tumor development in mice].
OBJECTIVE
To construct a dendritic cell vaccine transduced by murine alpha-fetoprotein (mAFP) gene, and evaluate its immunoprotective effect on C57BL/6J mice during the induction of hepatocellular carcinoma by diethylnitrosamines, carbon tetrachloride and ethanol.


METHODS
Dendritic cells (DCs) were induced and augmented by murine IL-4 and GM-CSF, and transfected by recombinant adenovirus engineered with mAFP gene. Major MHC class I and II, B7.1 (CD80), B7.2 (CD86), CD18a, and CD54 molecules on DC were analyzed by FACS. 80 C57BL/6J male mice were randomly divided into 4 groups (20 mice per group): Simple DC inoculated group, pAdBM5-mAFP-DC inoculated group, pAdBM5-mAFP plasmid inoculated group, and PBS control group. They were immunized once with 5 x 10(5) DCs (0.1 ml)/mouse administered s. c. in the left flank or 100 mg pAdBMS-mAFP plasmid/mouse administered i. m. in the left tibialis anterior muscle. Inoculation was conducted once a week for 4 weeks after 3 times consecutive immunization initially. At the same time of immunization, DEN/CCl4/ethanol were given to induce hepatocellular carcinoma. Tumor incidence was assessed after 20 weeks.


RESULTS
A transgenic DC vaccine was successfully constructed and the mAFP transgenic DCs expressed high level molecules of major MHC class I and II , B7.1, B7.2, CD18a, and CD54. After the 20-week induction, the incidence of primary hepatocellular carcinoma (PLC) was 70.0% in simple DC inoculated group, 25.0% in pAdBMS-mAFP-DC inoculated group, 65.0% in pAdBM5-mAFP plasmid inoculated group, and 75.0% in PBS control group. There was a significant difference between group B and other groups (P < 0.05).


CONCLUSIONS
mAFP transgenic DC tumor vaccine inoculation may induce strong immunoprotection against liver carcinogenesis and tumor development and reduce PLC incidence induced by DEN/CCl4/ethanol.
Xie
Yu-An
YA
Biomedicine Research Center of Guangxi Cancer Institute, Nanning 530021, China.
Kuang
Zhi-Peng
ZP
Liang
An-Min
AM
Luo
Xiao-Ling
XL
Yang
Fan
F
Wu
Ji-Ning
JN
D000256:Adenoviridae / Q000235:genetics*; D000818:Animals; D018122:B7-1 Antigen / Q000378:metabolism; D019496:Cancer Vaccines; D002251:Carbon Tetrachloride; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D004052:Diethylnitrosamine; D000431:Ethanol; D005822:Genetic Vectors; D015395:Histocompatibility Antigens Class I / Q000378:metabolism; D000949:Histocompatibility Antigens Class II / Q000378:metabolism; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D008114:Liver Neoplasms, Experimental / Q000139:chemically induced / Q000276:immunology / Q000517:prevention & control*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D011897:Random Allocation; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D014162:Transfection; D000509:alpha-Fetoproteins / Q000235:genetics* / Q000378:metabolism
D018122:B7-1 Antigen; D019496:Cancer Vaccines; D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II; D011994:Recombinant Proteins; D000509:alpha-Fetoproteins; D018799:Intercellular Adhesion Molecule-1; D004052:Diethylnitrosamine; D000431:Ethanol; D002251:Carbon Tetrachloride