OBJECTIVETo study the anti-tumor immunotherapeutic effect induced by the suicidalcancer vaccine FC/TK, and to evaluate the safety of this vaccine.

METHODSThe suicidal cancer vaccine, named FC/TK, was prepared by fusion of suicide gene (HSVI,-TK gene) -modified ovarian carcinoma NuTu-19 cells with rat bone marrow-derived dendritic cells (DCs). The morphology of FC/TK was evaluated by scanning electron microscopy. The stimulatory effect of FC/TK on T cells was determined by T cell proliferation assay. In immunotherapeutic studies in vivo, Fischer344 rats were injected subcutaneously with NuTu-19 cells, followed by treatment of FC/TK on days 7 and 14, compared to controls treated with irradiated FC/TK, FC or PBS, respectively. Tumor incidence and volume were measured in 90 days after challenge. To determine the killing effect of FC/TK in vivo, TUNEL assays were applied to detect apoptotic cell death in spleen of vaccinated rats with prodrug ganciclovir administration.

RESULTSFC/TK cells were of irregular shape with surface membrane processes. Compared to the control groups, FC/TK significantly promoted T cell proliferation (P <0.01). The rats vaccinated with FC/TK and FC significantly inhibited the tumor growth compared to rats vaccinated with irradiated FC/TK (P <0.05) or with PBS ( P <0.01). The immunotherapeutic effect induced by FC/TK was similar to that using FC. Fluorescence microscopy showed that fluorescein-stained FC/TK cells migrated into spleen also showed to be TUNEL-positive, suggesting that the FC/TK cells were killed by ganciclovir in vivo.

CONCLUSIONOur data indicate that suicidal cancer vaccine is an effective and safe therapy for ovarian carcinoma and may serve as a broadly applicable approach for other cancer vaccines in the future.

Animals ; Apoptosis ; drug effects ; Cancer Vaccines ; immunology ; Cell Fusion ; Cell Line, Tumor ; Cell Proliferation ; drug effects ; Dendritic Cells ; cytology ; immunology ; Female ; Ganciclovir ; pharmacology ; Genes, Transgenic, Suicide ; Herpesvirus 1, Human ; enzymology ; genetics ; Immunotherapy ; methods ; Microscopy, Electron, Scanning ; Microscopy, Fluorescence ; Neoplasms, Experimental ; enzymology ; pathology ; therapy ; Ovarian Neoplasms ; enzymology ; pathology ; therapy ; Rats ; Rats, Inbred F344 ; Survival Analysis ; T-Lymphocytes ; drug effects ; metabolism ; pathology ; Thymidine Kinase ; genetics ; metabolism ; Transfection