Therapeutic antitumor response to cervical cancer in mice immunized with U14 vaccines 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.
Tao
G
G
Department of Obstetrics & Gynecology, Second Affiliated Hospital, Hunan Medical University, Changsha 410011, China. gshtao@public.cs.hn.cn
Hu
J
J
Zou
H
H
Lin
Q
Q
Liu
F
F
Wu
Y
Y
Sun
Q
Q
D000818:Animals; D018122:B7-1 Antigen / Q000235:genetics* / Q000378:metabolism; D015139:Blotting, Southern; D019496:Cancer Vaccines / Q000235:genetics / Q000276:immunology*; D002455:Cell Division / Q000276:immunology; D002999:Clone Cells; D004247:DNA / Q000235:genetics; D005260:Female; D015870:Gene Expression; D007150:Immunohistochemistry; D051379:Mice; D010957:Plasmids / Q000235:genetics; D012313:RNA / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013154:Spleen / Q000166:cytology / Q000276:immunology; D014162:Transfection; D014407:Tumor Cells, Cultured; D002583:Uterine Cervical Neoplasms / Q000235:genetics / Q000276:immunology* / Q000473:pathology
D018122:B7-1 Antigen; D019496:Cancer Vaccines; D012313:RNA; D004247:DNA