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Increased oncolytic efficacy for high-grade gliomas by optimal integration of ionizing radiation into the replicative cycle of HSV-1

Gene Therapy volume 18, pages 1098–1102 (2011)Cite this article

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Abstract

Oncolytic viruses have been combined with standard cancer therapies to increase therapeutic efficacy. Given the sequential activation of herpes viral genes (herpes simplex virus-1, HSV-1) and the temporal cellular changes induced by ionizing radiation, we hypothesized an optimal temporal sequence existed in combining oncolytic HSV-1 with ionizing radiation. Murine U-87 glioma xenografts were injected with luciferase encoding HSV-1, and ionizing radiation (IR) was given at times before or after viral injection. HSV-1 replication and tumor-volume response were followed. Radiation given 6–9 h after HSV-1 injection resulted in maximal viral luciferase expression and infectious viral production in tumor xenografts. The greatest xenograft regression was also seen with radiation given 6 h after viral injection. We then tested if HSV-1 replication had a dose response to ionizing radiation. HSV-1 luciferase expression exhibited a dose response as xenografts were irradiated from 0 to 5 Gy. There was no difference in viral luciferase expression as IR dose increased from 5 Gy up to 20 Gy. These results suggest that the interaction of IR with the HSV-1 lytic cycle can be manipulated for therapeutic gain by delivering IR at a specific time within viral replicative cycle.

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Acknowledgements

This research was supported from grants from the US National Institutes of Health, CA 071933 and CA 097247. We thank Jennifer Coleman for assistance with manuscript preparation.

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Authors and Affiliations

  1. Department of Radiation Oncology and Center for Advanced Radiotherapy Technologies, Moores Cancer Center, University of California, San Diego, La Jolla, CA, USA

    S J Advani

  2. Department of Surgery, Division of Neurosurgery, University of Alabama at Birmingham, Birmingham, AL, USA

    J M Markert & G Y Gillespie

  3. Department of Radiation Oncology, The University of Chicago, Chicago, IL, USA

    R F Sood, M Y Shao & R R Weichselbaum

  4. Department of Radiology, University of Alabama at Birmingham, Birmingham, AL, USA

    S Samuel

  5. Marjorie B Kovler Viral Oncology Laboratories, The University of Chicago, Chicago, IL, USA

    B Roizman

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  1. S J Advani
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Correspondence to S J Advani.

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Advani, S., Markert, J., Sood, R. et al. Increased oncolytic efficacy for high-grade gliomas by optimal integration of ionizing radiation into the replicative cycle of HSV-1. Gene Ther 18, 1098–1102 (2011). https://doi.org/10.1038/gt.2011.61

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