IMMUNE RESPONSES INDUCED BY HepG2 CELLS EXPRESSING B7-1 OR IL-12 MOLECULES_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

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Department of Hepatobiliary Surgery, The First Affiliated Hospital, Sun Yat-sen University of Medical Sciences, Guangzhou 510080;

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Keywords：

B7 gene Interleukin 12 Liver neoplasm Immunotherapy Gene transfer

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Objective To investigate the effect of B7-1 and IL-12 gene expression on the immunogenicity of hepatocellular carcinoma (HCC) HepG2 cells.
Methods Plasmids encoding B7-1 and IL-12 molecules were retrovirally introduced into human HCC cells,empty vector as control. PBLs were cocultured with HepG2/B7-1,HepG2/IL-12 and HepG2/neo cells. Three days later,PBLs were submitted to specific cytotoxicity test and nonspecific cytotoxicity test against K562 cells by MTT assay.
Results HLA-Ⅰ molecules on PBLs were detected by FACS.HLA-Ⅰ molecules expressing on PBL cocultured with HepG2/B7-1,HepG2/IL-12 cells were enhanced by 16.95% and 14.71% than those of HepG2/neo group, respectively(Ｐ＜0.05). Specific cytotoxicity against HepG2/B7-1 cells was 12.5% higher than that of against HepG2/neo cell,while no increase in that of against HepG2/IL-12 cells. Cytotoxicities against K562 cells in HepG2/B7-1,HepG2/IL-12 groups were 19.38% and 14.78% higher than those of HepG2/neo group, but no significant difference between the first two groups.
Conclusion B7-1 and IL-12 gene transfer could remarkably promote immunogenicity of hepatocellular carcinoma cells and induce b specific and nonspecific immunity against hepatocellular carcinoma in vitro.

Citation： LU.. Mingde,ZHENG Yun,HUANG Jialing,et al.. IMMUNE RESPONSES INDUCED BY HepG2 CELLS EXPRESSING B7-1 OR IL-12 MOLECULES. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2000, 7(4): 208-210. doi: Copy

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9.	Lanzavecchia A. Identifying strategies for immune intervention 〔Ｊ〕. Science, 1993; 260(5)∶937.
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11.	Tanaka K, Gorelik E, Watanabe M, et al. Rejection of B16 melanoma induced by expression of a transfected major hostocompatibility complex class Ⅰ gene 〔Ｊ〕. Mol Cell Biol, 1988; 8(10)∶1857.
12.	Katsanis E, Xu Z, Bausero MA, et al. B71 expression decreases tumorigenicity induces partial systemic immunity to murine neuroblastoma deficient in major histocompatibility complex and costimulatory molecule 〔Ｊ〕. Cancer Gene Ther, 1995; 2(1)∶39.

1. Putzer BM, Hitt M, Muller WJ, et al. Interleukin12 and B71 costimulatory molecule expressed by an adenovirus vector act synergistically to facilitate tumor regression 〔Ｊ〕. Proc Natl Acad Sci, 1997; 94(20)∶10889.
2. Yang G, Hellstrom KE, Hellstrom I, et al. Antitumor immunity elicited by tumor cells transfected with B72, a second ligand for CD28/CTLA4 costimulatory molecules 〔Ｊ〕. J Immunol, 1995; 154(6)∶2794.
3. Zitvogel L, Tahara H, Cai Q, et al. Construction and characterization of retroviral vectors expressing biologically active human interleukin12 〔Ｊ〕. Hum Gene Ther, 1994; 5(12)∶1493.
4. 〔美〕J.萨姆布鲁克， E.F.费里奇， T.曼尼阿蒂斯著. 黎孟枫，金冬雁译. 分子克隆实验指南〔M〕. 第2版. 北京：科学出版社， 1996∶16～18.
5. Jung D, Jaeger E, Cayeux S, et al. Strong immunogenic potential of a B7 retroviral expression vector: generation of HLAB7restricted CTL response against selectable marker genes 〔Ｊ〕. Hum Gene Ther, 1998; 9(1)∶53.
6. Paroli M, Perrone, Bonaoita MS. Immunology of hepatocellular carcinoma 〔Ｊ〕. Ital J Gastroenterol, 1991; 23(3)∶494.
7. Carroll MW, Overwijk WW, Surman DR, et al. Construction and characterization of a triplerecombinant vaccinia virus encoding B71, interleukin 12, and a model tumor antigen 〔Ｊ〕. J Natl Cancer Inst, 1998; 90(24)∶1881.
8. Brunda MJ, Cavallo F, Signorelli P, et al. Antitumor efficiency of adenocarcinoma cells engineered to produce interleukin12 (IL12) or other cytokines compared with exogenous IL12 〔Ｊ〕. J Natl Cancer Inst, 1997; 89(6)∶10493.
9. Lanzavecchia A. Identifying strategies for immune intervention 〔Ｊ〕. Science, 1993; 260(5)∶937.
10. Garrido F, Cabrera T, Concha, et al. Natural history of HLA expression during tumor development 〔Ｊ〕. Immunol Today, 1993; 14(3)∶491.
11. Tanaka K, Gorelik E, Watanabe M, et al. Rejection of B16 melanoma induced by expression of a transfected major hostocompatibility complex class Ⅰ gene 〔Ｊ〕. Mol Cell Biol, 1988; 8(10)∶1857.
12. Katsanis E, Xu Z, Bausero MA, et al. B71 expression decreases tumorigenicity induces partial systemic immunity to murine neuroblastoma deficient in major histocompatibility complex and costimulatory molecule 〔Ｊ〕. Cancer Gene Ther, 1995; 2(1)∶39.

CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

IMMUNE RESPONSES INDUCED BY HepG2 CELLS EXPRESSING B7-1 OR IL-12 MOLECULES

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