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Combination of the oncolytic adenovirus ICOVIR-5 with chemotherapy provides enhanced anti-glioma effect in vivo

Cancer Gene Therapy volume 14, pages 756–761 (2007)Cite this article

Abstract

Novel therapies are clearly needed for gliomas, and the combination of oncolytic vectors with chemotherapy possesses a significant hope for the treatment of this malignancy. In addition, combination with chemotherapy allows for lower virus doses to achieve anticancer effect, thus resulting in lower undesirable toxicities due to viral proteins. In this work, we sought to determine whether combination of an oncolytic adenovirus ICOVIR-5, with RAD001 or temozolomide (TMZ) could result in enhanced anti-glioma effect in vivo. We assessed the in vitro cytotoxic effect and replication properties of ICOVIR-5 in combination with RAD001 or TMZ in U87 MG glioma cell line by MTT and TCID50, respectively. Our data showed that in vitro treatment with RAD001 or TMZ not only interfered with adenovirus replication but, in addition, enhanced its oncolytic properties. To evaluate the in vivo anticancer effect, athymic mice bearing glioma xenografts (5 × 105 U87 MG cells/animal) received a single intratumoral injection of ICOVIR-5 (107 PFU/animal). RAD001 was given as a regimen of 5 mg/kg 5 days per week until the end of the experiment and TMZ was administered for 5 days at 7.5 mg/kg/mice. Of significance, combination of ICOVIR-5 with RAD001 or TMZ showed a potent anti-glioma effect in vivo, resulting in a dramatic extension of the median animal survival and in 20–40% animals becoming free of disease beyond 90 days.

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Acknowledgements

We thank Verlene Henry and Jennifer Edge for technical assistance with the animal experiments, and Betty P Notzon (Department of Scientific Publications, University of Texas MD Anderson Cancer Center) for editorial assistance. This work was supported by the National Cancer Institute RO1 CA90879 (JF). MMA is supported by the American Brain Tumor Association (ABTA) ‘Harper Rowland’ fellowship.

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Authors and Affiliations

  1. Department of Neuro-oncology, University of Texas MD Anderson Cancer Center, Houston, TX, USA

    M M Alonso, C Gomez-Manzano, H Jiang, Y Piao, W K A Yung & J Fueyo

  2. Department of Biostatistics, University of Texas MD Anderson Cancer Center, Houston, TX, USA

    N B Bekele

  3. Translational Research Laboratory, Institut Catala d'Oncologia Barcelona, Barcelona, Spain

    R Alemany

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  1. M M Alonso
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  2. C Gomez-Manzano
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  3. H Jiang
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  6. W K A Yung
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  8. J Fueyo
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Correspondence to J Fueyo.

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Supplementary Information accompanies the paper on Cancer Gene Therapy website (http://www.nature.com/cgt)

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Alonso, M., Gomez-Manzano, C., Jiang, H. et al. Combination of the oncolytic adenovirus ICOVIR-5 with chemotherapy provides enhanced anti-glioma effect in vivo. Cancer Gene Ther 14, 756–761 (2007). https://doi.org/10.1038/sj.cgt.7701067

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