Send to

Choose Destination
Int J Oncol. 2011 Mar;38(3):871-8. doi: 10.3892/ijo.2011.910. Epub 2011 Jan 18.

Vaccinia virus GLV-1h237 carrying a Walker A motif mutation of mouse Cdc6 protein enhances human breast tumor therapy in mouse xenografts.

Author information

Department of Biochemistry, Biocenter, University of Würzburg, Würzburg, Germany.


Recently it was shown that recombinant vaccinia virus GLV-1h68 is a promising tool for treating different type of cancers in animal models. The goal of the present study was to enhance the oncolytic potential of GLV-1h68 without decreasing its safety. A derivative of GLV-1h68 containing the gene for a Walker A motif mutant of the essential cell cycle protein Cdc6, GLV-1h237, was engineered. The characteristics of GLV-1h237 and its efficiency in treating human breast cancer GI-101A cells were compared with that of GLV-1h236 (carrying the wild-type gene for Cdc6), GLV-1h71 (a derivative of GLV-1h68) and GLV-1h68, respectively. RT-PCR and immunoblot analyses revealed that Cdc6 is efficiently overexpressed in GLV-1h237-infected GI-101A cells. GLV-1h237 was found to have higher replication efficiency and enhanced cytotoxity than GLV-1h68 in cell culture. In the GI-101A tumor xenograft animal model, GLV-1h237 turned out to be the most potent oncolytic virus strain investigated. A single i.v. injection of GLV-1h237 resulted in enhanced anti-tumor activity compared to GLV-1h68 concomitant with a high tumor selectivity and a comparable safety profile. Thus, the strategy to combine oncolytic virotherapy with agents that interfere with host cell DNA synthesis is a promising approach for effective cancer therapy.

[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Spandidos Publications
Loading ...
Support Center