[Suicidal cancer vaccine enhances anti-tumor immunotherapeutic effect and its safety in the treatment of ovarian cancer].
OBJECTIVE
To study the anti-tumor immunotherapeutic effect induced by the suicidalcancer vaccine FC/TK, and to evaluate the safety of this vaccine.


METHODS
The 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.


RESULTS
FC/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.


CONCLUSIONS
Our 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.
Kang
Yu
Y
Department of Gynecology, Obstetrics and Gynecology Hospital, Fudan University, Shanghai 200011, China.
Xu
Cong-jian
CJ
Liu
Xi-shi
XS
Shao
Zhi-min
ZM
Ou
Zhou-luo
ZL
Luo
Jian-ming
JM
Wu
Chao-qua
CQ
Zhong
Cui-ping
CP
Gu
Jian-ren
JR
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D019496:Cancer Vaccines / Q000276:immunology; D002459:Cell Fusion; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology; D005260:Female; D015774:Ganciclovir / Q000494:pharmacology; D041722:Genes, Transgenic, Suicide; D018259:Herpesvirus 1, Human / Q000201:enzymology / Q000235:genetics; D007167:Immunotherapy / Q000379:methods*; D008855:Microscopy, Electron, Scanning; D008856:Microscopy, Fluorescence; D009374:Neoplasms, Experimental / Q000201:enzymology / Q000473:pathology / Q000628:therapy; D010051:Ovarian Neoplasms / Q000201:enzymology / Q000473:pathology / Q000628:therapy*; D051381:Rats; D011916:Rats, Inbred F344; D016019:Survival Analysis; D013601:T-Lymphocytes / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D013937:Thymidine Kinase / Q000235:genetics / Q000378:metabolism*; D014162:Transfection
D019496:Cancer Vaccines; D013937:Thymidine Kinase; D015774:Ganciclovir