Prevention of hepatocellular carcinoma in mice by IL-2 and B7-1 genes co-transfected liver cancer cell vaccines.
OBJECTIVE
To study the immunoprotective effect of liver cancer vaccine with co-transfected IL-2 and B7-1 genes on hepatocarcinogenesis in mice.


METHODS
The murine liver cancer cell line Hepal-6 was transfected with IL-2 and/or B7-1 gene via recombinant adenoviral vectors and the liver cancer vaccines were prepared. C57BL/6 mice were immunized with these vaccines and challenged with the parental Hepal-6 cells afterwards. The immunoprotection was investigated and the reactive T cell line was assayed.


RESULTS
The immunoprotection of the tumor vaccine was demonstrated. The effect of IL-2 and B7-1 genes co-transfected Hepal-6 liver cancer vaccine (Hep6-IL2/B7 vaccine) on the onset of tumor formation was the strongest. When attacked with wild Hepal-6 cells, the median survival period of the mice immunized with Hep6-IL2/B7 vaccine was the longest (68 days, chi2=7.70-11.69, P<0.05) and the implanted tumor was the smallest (z =3.20-44.10, P<0.05). The effect of single IL-2 or B7-1 gene-transfected vaccine was next to the IL2/B7 gene co-transfected group, and the mean survival periods were 59 and 54 days, respectively. The mean survival periods of wild or enhanced green fluorescence protein gene modified vaccine immunized group were 51 and 48 days, respectively. The mice in control group all died within 38 days and the implanted tumor was the largest (z=3.20-40.21, P<0.05). The cellular immunofunction test and cytotoxicity study showed that the natural killer (NK) cell, lymphokine activated killer (LAK) cell and cytotoxic T lymphocyte (CTL) activities were significantly increased in mice immunized with the Hep6-IL2/B7 vaccine, (29.5+/-2.5 %, 65.0+/-2.9 %, 83.1+/-1.5 % respectively, compared with other groups, P<0.05).


CONCLUSIONS
The Hep6-IL2/B7 liver cancer vaccines can induce the mice to produce activated and specific CTL against the parental tumor cells, and demonstrate stronger effect on the hepatocarcinogenesis than single gene modified or the regular tumor vaccine. Therefore, the vaccines may become a novel potential therapy for recurrence and metastasis of HCC.
Ge
Ning-Ling
NL
Liver Cancer Institute of Zhongshan Hospital Affiliated to Fudan University, Shanghai 200032, China.
Ye
Sheng-Long
SL
Zheng
Ning
N
Sun
Rui-Xia
RX
Liu
Yin-Kun
YK
Tang
Zhao-You
ZY
D000818:Animals; D018122:B7-1 Antigen / Q000235:genetics*; D019496:Cancer Vaccines / Q000235:genetics*; D006528:Carcinoma, Hepatocellular / Q000276:immunology / Q000517:prevention & control*; D045744:Cell Line, Tumor; D005260:Female; D005434:Flow Cytometry; D015870:Gene Expression; D015316:Genetic Therapy; D007376:Interleukin-2 / Q000235:genetics*; D007694:Killer Cells, Natural / Q000276:immunology; D008114:Liver Neoplasms, Experimental / Q000276:immunology / Q000517:prevention & control*; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D013154:Spleen / Q000166:cytology; D014162:Transfection
D018122:B7-1 Antigen; D019496:Cancer Vaccines; D007376:Interleukin-2