Anti-gastric cancer active immunity induced by FasL/B7-1 gene-modified tumor cells.
OBJECTIVE
To study the activation of cytotoxic T lymphocytes (CTLs) against gastric cancer cells induced by FasL/B7-1 (FB-11) gene-modified tumor cells, and to explore whether co-expression of FasL and B7-1 in SGC-7901 tumor cells could initiate synergistic antitumor effect.


METHODS
FasL and B7-1 genes were transfected into human SGC-7901 gastric cancer cells with adenovirus vectors. The positive clones were selected by G418. FasL and B7-1 genes were detected by flow cytometry and RT-PCR. Abdominal infiltrating lymphocytes and sensitized spleen cells were obtained from mice that were immunized with SGC-7901/FB-11 or wild type SGC-7901 cells intraperitoneally, and cytotoxicity of these CTLs against tumor cells was determined by MTT assay.


RESULTS
Flow cytometry and RT-PCR showed that FasL and B7-1 genes were highly expressed. FasL and B7-1 transfected cancer cells had a high apoptosis index. DNA laddering suggested that FasL and B7-1 genes induced gastric cancer cell apoptosis. FasL(+)/B7-1(+)SGC-7901 cells (SGC-7901/FB-11) were inoculated subcutaneously in the dorsal skin of C57BL/6 mice and then decreased their tumorigenicity greatly (z = 2.15-46.10, P<0.01). SGC-7901/FB-11 cell-sensitized mice obtained protective immune activity against the rechallenge of wild type SGC-7901 cells (z = 2.06-44.30, P<0.05). The cytotoxicity of CTLs induced by SGC-7901/FB-11 cells against SGC-7901 was significantly higher than that of CTLs activated by wild-type SGC-7901 cells (84.1+/-2.4% vs 30.5+/-2.3%, P<0.05).


CONCLUSIONS
FasL and B7-1 genes can effectively promote the activity of CTLs against gastric cancer cells. FasL/B7-1 molecules play an important role in CTL cytotoxicity.
Zheng
Shi-Ying
SY
Department of Cardiothoracic Surgery, The First Affiliated Hospital of Suzhou University, Suzhou 215006, Jiangsu Province, China. syzheng88@ sina.com
Li
De-Chun
DC
Zhang
Zhi-De
ZD
Zhao
Jun
J
Ge
Jin-Feng
JF
D000818:Animals; D018122:B7-1 Antigen / Q000235:genetics* / Q000276:immunology; D045744:Cell Line, Tumor; D053222:Fas Ligand Protein; D015316:Genetic Therapy / Q000379:methods*; D006801:Humans; D007167:Immunotherapy / Q000379:methods; D007668:Kidney / Q000166:cytology; D008562:Membrane Glycoproteins / Q000235:genetics* / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D013274:Stomach Neoplasms / Q000276:immunology* / Q000628:therapy*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
D018122:B7-1 Antigen; C505661:FASLG protein, human; D053222:Fas Ligand Protein; C505658:Fasl protein, mouse; D008562:Membrane Glycoproteins