Suicidal cancer vaccine enhances anti-tumor immunotherapeutic effect and its safety in the treatment of ovarian cancer.
- Author:
Yu KANG
1
;
Cong-jian XU
;
Xi-shi LIU
;
Zhi-min SHAO
;
Zhou-luo OU
;
Jian-ming LUO
;
Chao-qua WU
;
Cui-ping ZHONG
;
Jian-ren GU
Author Information
- Publication Type:Journal Article
- MeSH: 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
- From: Chinese Journal of Oncology 2006;28(9):654-657
- CountryChina
- Language:Chinese
-
Abstract:
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.