title: Therapeutic antitumor response to cervical cancer in mice immunized with U14 vaccines transfected with costimulatory B7 gene.
abstract: 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.
authors.affiliation: Department of Obstetrics & Gynecology, Second Affiliated Hospital, Hunan Medical University, Changsha 410011, China. gshtao@public.cs.hn.cn
authors.forename: G
authors.initials: G
authors.lastname: Tao
authors.forename: J
authors.initials: J
authors.lastname: Hu
authors.forename: H
authors.initials: H
authors.lastname: Zou
authors.forename: Q
authors.initials: Q
authors.lastname: Lin
authors.forename: F
authors.initials: F
authors.lastname: Liu
authors.forename: Y
authors.initials: Y
authors.lastname: Wu
authors.forename: Q
authors.initials: Q
authors.lastname: Sun
mesh_terms: 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
chemical_list: D018122:B7-1 Antigen; D019496:Cancer Vaccines; D012313:RNA; D004247:DNA