These tools will no longer be maintained as of December 31, 2024. Archived website can be found here. PubMed4Hh GitHub repository can be found here. Contact NLM Customer Service if you have questions.


Pubmed for Handhelds

PUBMED FOR HANDHELDS

Search MEDLINE/PubMed

  • Title: [Herpes simplex virus type 1 thymidine kinase/ganciclovir (HSV(1)-TK/GCV) system as an effective "in vivo death switch" of live tumor vaccines].
    Author: Kang Y, Xu CJ, Liu XS, Wu CQ, Zhong CP, Gu JR.
    Journal: Ai Zheng; 2005 Aug; 24(8):909-14. PubMed ID: 16086864.
    Abstract:
    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.
    [Abstract] [Full Text] [Related] [New Search]