Liver Cancer
Copyright ©The Author(s) 2003. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Oct 15, 2003; 9(10): 2182-2185
Published online Oct 15, 2003. doi: 10.3748/wjg.v9.i10.2182
Prevention of hepatocellular carcinoma in mice by IL-2 and B7-1 genes co-transfected liver cancer cell vaccines
Ning-Ling Ge, Sheng-Long Ye, Ning Zheng, Rui-Xia Sun, Yin-Kun Liu, Zhao-You Tang
Ning-Ling Ge, Sheng-Long Ye, Ning Zheng, Rui-Xia Sun, Yin-Kun Liu, Zhao-You Tang, Liver Cancer Institute of Zhongshan Hospital Affiliated to Fudan University, Shanghai 200032, China
Author contributions: All authors contributed equally to the work.
Supported by the National Key Technologies Research and Development during the 9th Five-Year Plan period, Program of China, No. 96-906-01-20
Correspondence to: Dr. Sheng-Long Ye, Liver Cancer Institute of Zhongshan Hospital Affiliated to Fudan University, Shanghai 200032, China. slye@shmu.edu.cn
Telephone: +86-21-64041990 Ext 2150 Fax: +86-21-64037181
Received: May 12, 2003
Revised: May 25, 2003
Accepted: June 2, 2003
Published online: October 15, 2003
Abstract

AIM: 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 d, χ2 = 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 d, respectively. The mean survival periods of wild or enhanced green fluorescence protein gene modified vaccine immunized group were 51 and 48 d, respectively. The mice in control group all died within 38 d 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).

CONCLUSION: 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.

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