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Combination effect of oncolytic adenovirotherapy and TRAIL gene therapy in syngeneic murine breast cancer models

Cancer Gene Therapy volume 13, pages 82–90 (2006)Cite this article

Abstract

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) gene therapy and oncolytic adenovirotherapy have been investigated extensively in xenografic human tumor models established in immunocompromised nude mice. However, the effects of these therapies on syngeneic murine tumors in immunocompetent settings were not well documented. We hypothesized that TRAIL gene therapy used with an oncolytic adenovirus would overcome the weaknesses of the two therapies used individually. In this study, we evaluated the antitumor effects of an oncolytic adenovirus, Delta24, in both human and murine breast cancer cell lines. We also analyzed the effects of TRAIL gene therapy combined with oncolytic virotherapy in these cancer cells. Our results showed that Delta24 can replicate and help the E1-deleted adenovector replicate in murine cancer cells. We also found that these two therapies combined had greater antitumor activity than either one alone in both human and murine breast cancer cells lines and in the syngeneic breast cancer models established in immunocompetent mice. Moreover, Delta24 virotherapy alone and combined with TRAIL gene therapy dramatically reduced the spontaneous liver metastasis that originated in the subcutaneous 4T1 tumor established in Balb/c mice. These findings provide important considerations in the development and preclinical assessments of oncolytic virotherapy.

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Acknowledgements

We thank Henry Peng and Li Wang for propagating the adenovirus and conducting the vector quality test, Alma J Vega for helping prepare the manuscript, and Gayle Nesom for reviewing the manuscript. This article represents the partial fulfillment of the requirements for a PhD for JJ Davis. This work was supported in part by National Cancer Institute grants RO1 CA 092487-01A1 (to B Fang), RO1 CA 098582-01A1 (to B Fang), and CA-16672 and by the Lockton grant-matching fund.

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Authors and Affiliations

  1. Department of Thoracic and Cardiovascular Surgery, The University of Texas MD Anderson Cancer Center, Houston, 77030, TX, USA

    W Guo, H Zhu, L Zhang, J Davis, F Teraishi, J A Roth & B Fang

  2. Department of Surgical Oncology, Sir Run Run Shaw Hospital, Zhejiang University, China

    H Zhu

  3. Program in Gene Therapy and Virology, The University of Texas Graduate School of Biomedical Sciences, Houston, 77030, TX, USA

    J Davis & B Fang

  4. Veterinary Medicine & Surgery, The University of Texas MD Anderson Cancer Center, Houston, 77030, TX, USA

    C Stephens

  5. Neuro-Oncology, The University of Texas MD Anderson Cancer Center, Houston, 77030, TX, USA

    J Fueyo, H Jiang & C Conrad

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  1. W Guo
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  2. H Zhu
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  11. B Fang
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Correspondence to B Fang.

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Guo, W., Zhu, H., Zhang, L. et al. Combination effect of oncolytic adenovirotherapy and TRAIL gene therapy in syngeneic murine breast cancer models. Cancer Gene Ther 13, 82–90 (2006). https://doi.org/10.1038/sj.cgt.7700863

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  • DOI: https://doi.org/10.1038/sj.cgt.7700863

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