PMID- 16086864
OWN - NLM
STAT- MEDLINE
DCOM- 20070216
LR  - 20150313
VI  - 24
IP  - 8
DP  - 2005 Aug
TI  - [Herpes simplex virus type 1 thymidine kinase/ganciclovir (HSV(1)-TK/GCV) system 
      as an effective "in vivo death switch" of live tumor vaccines].
PG  - 909-14
AB  - BACKGROUND & OBJECTIVE: Live tumor vaccines could achieve better 
      immunotherapeutic effects than irradiated tumor vaccines; however, the 
      tumorigenicity is the crucial drawback incurred by the current procedures for 
      vaccine preparation. This study was to explore the application of herpes simplex 
      virus type 1 thymidine kinase/ganciclovir (HSV1-TK/GCV) system as "in vivo death 
      switch" to control the survival status of cancer vaccines under certain 
      circumstances. METHODS: Suicide gene HSV(1)-TK was transferred into ovarian 
      cancer cell line NuTu-19 with a retrovirus vector, followed by G418 selection to 
      obtain HSV(1)-TK-transfected NuTu-19 cells (NuTu-19/TK). Dendritic cells (DCs) 
      derived from Fischer344 rat bone marrow were fused with NuTu-19/TK cells to 
      construct live tumor vaccine FC/TK. The expression of HSV(1)-TK in FC/TK cells 
      was determined by reverse transcription-polymerase chain reaction (RT-PCR) and 
      Western blot. The cytotoxic efficacy of GCV on FC/TK cells was evaluated by XTT 
      assay. The apoptosis of FC/TK cells was analyzed by flow cytometry and 
      Hoechst33258 staining after GCV treatment. Rats were vaccinated with FC/TK cells 
      and divided into 2 groups: GCV group (5 rats) were intraperitoneally treated with 
      GCV for 7 days, control group (5 rats) were treated with normal saline. The 
      tumorigenesis and tumor metastasis in the rats were observed 90 days after 
      inoculation. RESULTS: HSV1-TK was specifically expressed in FC/TK cells. GCV 
      showed in vitro cytotoxicity to FC/TK cells in a dose-dependent manner, and 
      86.25% of the FC/TK cells were killed by GCV at a concentration of 100 microg/ml; 
      the apoptosis rate of FC/TK cells was over 80%, and apoptotic morphology, 
      including cell shrinkage, chromatin condensation, was observed. In the rat 
      models, the tumor was developed at the injection site in 3 rats of control group, 
      while no tumor was observed in the rats of GCV group. CONCLUSION: HSV(1)-TK/GCV 
      could act as the "death switch" of tumor vaccines by triggering apoptosis of 
      tumor vaccines both in vitro and in vivo.
FAU - Kang, Yu
AU  - Kang Y
AD  - Department of Obstetrics and Gynecology, Obstetrics and Gynecology Hospital, 
      Fudan University, Shanghai 200011, P. R. China.
FAU - Xu, Cong-Jian
AU  - Xu CJ
FAU - Liu, Xi-Shi
AU  - Liu XS
FAU - Wu, Chao-Qun
AU  - Wu CQ
FAU - Zhong, Cui-Ping
AU  - Zhong CP
FAU - Gu, Jian-Ren
AU  - Gu JR
LA  - chi
PT  - English Abstract
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - China
TA  - Ai Zheng
JT  - Ai zheng = Aizheng = Chinese journal of cancer
JID - 9424852
RN  - 0 (Cancer Vaccines)
RN  - EC 2.7.1.21 (Thymidine Kinase)
RN  - P9G3CKZ4P5 (Ganciclovir)
SB  - IM
MH  - Animals
MH  - Apoptosis/drug effects
MH  - *Cancer Vaccines
MH  - Cell Fusion
MH  - Dendritic Cells/cytology/enzymology
MH  - Female
MH  - Ganciclovir/*pharmacology
MH  - *Genes, Transgenic, Suicide
MH  - Genetic Vectors
MH  - Herpesvirus 1, Human/*enzymology/genetics
MH  - Immunotherapy, Active
MH  - Ovarian Neoplasms/enzymology/*pathology
MH  - Rats
MH  - Rats, Inbred F344
MH  - Retroviridae/genetics
MH  - Thymidine Kinase/genetics/*metabolism
MH  - Transfection
MH  - Tumor Cells, Cultured
EDAT- 2005/08/10 09:00
MHDA- 2007/02/17 09:00
CRDT- 2005/08/10 09:00
PHST- 2005/08/10 09:00 [pubmed]
PHST- 2007/02/17 09:00 [medline]
PHST- 2005/08/10 09:00 [entrez]
AID - 1000467X2005080909 [pii]
PST - ppublish
SO  - Ai Zheng. 2005 Aug;24(8):909-14.