Therapeutic antitumor response to cervical cancer in mice immunized with U14 v accines transfected with costimulatory B7 gene

OBJECTIVE: To investigate the effect of U14 vaccine transfected with the B7 gene in inducing antitumor immune response to murine cervical carcinoma in Chinese 615-strain mice. METHODS: A recombinant retroviral plasmid vector expressing mouse B7-1 gene (pLNSX-mB7) was transfected into 615-strain mouse cervical carcinoma cell line No. 14 (U14) by electroporation to set up a highly-expressed mB7-1 U14 cell clonal strain (B7+ U14). In vivo experiments: (1) B7+ U14 vaccine was primed to protect the 615-strain mice against U14 re-challenge. (2) B7+ U14 vaccine was injected into tumor-bearing mice with different tumor sizes. Lifetimes and tumor sizes were recorded. In vitro cytotoxicity assay: Mice were immunized with B7+ U14 or U14 vaccine and 2 weeks later, spleen cells of those mice were cultured for 2 days. The cytotoxicity of these cells against U14 was detected by 5-diphenyl tetrazolium bromide assay. RESULTS: We obtained several B7-1 high expression clonal U14 lines. In vivo experiment, we did not find tumor growing in 3 of the 6 mice primed by B7+ U14 vaccine during their entire life after re-challenge with U14. The other 3 mice developed tumors and their average survival time was longer than that of the control group (P < 0.01). All 6 mice grew tumors in the control group. When the transplanted tumors became palpable, the mice were randomly divided into 3 groups to be injected with B7+ U14 vaccine. It was effective for tumor-bearing mice only when the tumor diameters were < 3 mm. When the diameters were > or = 3 mm, it was not efficacious to inject B7+ U14 vaccine (P < 0.05). In vitro cytotoxicity assay, cytotoxic T lymphocytes induced by B7+ U14 vaccine had a higher cytotoxicity against U14 than that induced by U14 vaccine (F = 310.8, P < 0.001). CONCLUSIONS: Vaccines of cervical cancer cells transfected with the costimulatory molecule B7 gene can induce antitumor immune protection in host mice against U14 re-challenge. This treatment may cure part of the tumor-bearing mice but be restricted by tumor size. The results suggest that transfecting the B7 gene into cervical cancer as a cell vaccine may be an efficient supplementary method to treat cervical cancer after operation.