Experimental Study On Ovarian Cancer Immunotherapy By EpCAM Activated Dendritic Cells Induce Antigen-specific CD8+ Cytotoxic T Lymphocytes

Objective:To observe the effect on ovarian cancer immunotherapy by Epithelial cell adhesion molecule(EpCAM)activated dendritic cells(DC)induce antigen-specific CD8~+cytotoxic T lymphocytes(CTL)and offer help to ovarian cancer immunotherapy.Methods:After induce by EpCAM,surface molecules,interleukin(IL)-12 and IL-10 of DC were tested.Subsequently,EpCAM specific CTL CD8~+was induced by EpCAM-DC.The therapeutic effect and interferon(IFN)-?of EpCAM-DC-CD8~+CTL on normal ovarian epithelial cells IOSE80 and ovarian cancer cell SKOV3 was detected.After treatment of EpCAM-DC-CD8~+CTL,tumor volume of ovarian tumor of bearing BALB/C-nu/nu mice was detected.Meanwhile,the changes of tumor tissue were observed by HE staining.Results:Compared with PBS,EpCAM stimulation can significantly improve surface markers DC80,DC83,DC86 and HLA-DR levels,and up to 4.79,4.85,4.60,and 10.91times(P<0.05).EpCAM stimulation significantly increased the expression of IL-12and significantly reduced the secretion of IL-10(P<0.05).DC-CD8~+CTL and EpCAM-DC-CD8~+CTL both resulted in little amount of IOSE80 cell killing(P>0.05),but the killing rate of EpCAM-DC-CD8~+CTL on SKOV3 cells was 6.82-folds as much as that of DC-CD8~+CTL.Animal experiments showed that after EpCAM-DC-CD8~+CTL treatment,ovarian cancer transplantation tumor volume ratio was significantly lower than PBS group and DC-CD8~+CTL group,which reached 0.27 and 0.28 times,respectively(P<0.05).HE staining showed that EpCAM-DC-CD8~+CTL treatment resulted in significant pathological changes in tumor tissues.Conclusion:EpCAM protein stimulated the maturation of DC that induced the production of EpCAM specific CD8~+CTL.EpCAM-DC-CD8+CTL can effectively kill ovarian tumor cells and delay the growth of tumor,which is of great significance for the immunotherapy of ovarian cancer.