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

  • Authors:
    • Elisabeth Hofmann
    • Friedrich Grummt
    • Aladar A. Szalay
  • View Affiliations

  • Published online on: January 18, 2011     https://doi.org/10.3892/ijo.2011.910
  • Pages: 871-878
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Abstract

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.

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March 2011
Volume 38 Issue 3

Print ISSN: 1019-6439
Online ISSN:1791-2423

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APA
Hofmann, E., Grummt, F., & Szalay, A.A. (2011). Vaccinia virus GLV-1h237 carrying a Walker A motif mutation of mouse Cdc6 protein enhances human breast tumor therapy in mouse xenografts. International Journal of Oncology, 38, 871-878. https://doi.org/10.3892/ijo.2011.910
MLA
Hofmann, E., Grummt, F., Szalay, A. A."Vaccinia virus GLV-1h237 carrying a Walker A motif mutation of mouse Cdc6 protein enhances human breast tumor therapy in mouse xenografts". International Journal of Oncology 38.3 (2011): 871-878.
Chicago
Hofmann, E., Grummt, F., Szalay, A. A."Vaccinia virus GLV-1h237 carrying a Walker A motif mutation of mouse Cdc6 protein enhances human breast tumor therapy in mouse xenografts". International Journal of Oncology 38, no. 3 (2011): 871-878. https://doi.org/10.3892/ijo.2011.910