Gs. Tao et al., Therapeutic antitumor response to cervical cancer in mice immunized with U14 vaccines transfected with costimulatory B7 gene, CHIN MED J, 114(6), 2001, pp. 623-627
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 l
ine 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 w
as primed to protect the 615-strain mice against U14 re-challenge. (2) B7U14 vaccine was injected into tumor-bearing mice with different tumor sizes
. Lifetimes and tumor sizes were recorded. In vitro cytotoxicity assay: Mic
e were immunized with B7(+) U14 or U14 vaccine and 2 weeks later, spleen ce
lls 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 oth
er 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 contro
l group. When the transplanted tumors became palpable, the mice were random
ly divided into 3 groups to be injected with B7(+) U14 vaccine. It was effe
ctive for tumor-bearing mice only when the tumor diameters were < 3 mm. Whe
n the diameters were greater than or equal to 3 mm, it was not efficacious
to inject B7(+) U14 vaccine (P < 0.05). In vitro cytotoxicity assay, cytoto
xic T lymphocytes induced by B7(+) U14 vaccine had a higher cytotoxicity ag
ainst U14 than that induced by U14 vaccine ( F = 310.8, P < 0.001).
Conclusions Vaccines of cervical cancer cells transfected with the costimul
atory 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 transfectin
g the B7 gene into cervical cancer as a cell vaccine may be an efficient su
pplementary method to treat cervical cancer after operation.