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Radiation increases the activity of oncolytic adenovirus cancer gene therapy vectors that overexpress the ADP (E3-11.6K) protein

Cancer Gene Therapy volume 10, pages 193–200 (2003)Cite this article

Abstract

We have described three potential adenovirus type 5 (Ad5)-based replication-competent cancer gene therapy vectors named KD1, KD3, and VRX-007. All three vectors overexpress an Ad5 protein named Adenovirus Death Protein (ADP, also named E3–11.6 K protein). ADP is required for efficient lysis of Ad5-infected cells and spread of virus from cell to cell, and thus its overexpression increases the oncolytic activity of the vectors. KD1 and KD3 contain mutations in the Ad5 E1A gene that knock out binding of the E1A proteins to cellular p300/CBP and pRB; these mutations allow KD1 and KD3 to grow well in cancer cells but not in normal cells. VRX-007 has wild-type E1A. Here we report that radiation increases the oncolytic activity of KD1, KD3, and VRX-007. This increased activity was observed in cultured cells, and it was not because of radiation-induced replication of the vectors. The combination of radiation plus KD3 suppressed the growth of A549 lung adenocarcinoma xenografts in nude mice more efficiently than radiation alone or KD3 alone. The combination of ADP-overexpressing vectors and radiation may have potential in treating cancer.

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Acknowledgements

We thank Chris Wells and Meribeth Broadway for technical assistance. This research was supported by grants CA71704, CA58538, and CA81829 from the National Institutes of Health.

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Authors and Affiliations

  1. Department of Molecular Microbiology and Immunology, Saint Louis University School of Medicine, St Louis, 63104, Missouri, USA

    Karoly Toth, Vera Tarakanova, Konstantin Doronin, Peter Ward, Mohan Kuppuswamy & William S M Wold

  2. Department of Radiation Oncology, Washington University School of Medicine, 660 S. Euclid Ave., St Louis, 63110, Missouri, USA

    Jacob E Locke

  3. Department of Radiation Oncology, Saint Louis University School of Medicine, St Louis, 63104, Missouri, USA

    Julie E Dawson & Han J Kim

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  1. Karoly Toth
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Correspondence to Karoly Toth.

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Toth, K., Tarakanova, V., Doronin, K. et al. Radiation increases the activity of oncolytic adenovirus cancer gene therapy vectors that overexpress the ADP (E3-11.6K) protein. Cancer Gene Ther 10, 193–200 (2003). https://doi.org/10.1038/sj.cgt.7700555

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