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Treatment of Implantable NF2 Schwannoma Tumor Models with Oncolytic Herpes Simplex Virus G47Δ

Cancer Gene Therapy volume 14, pages 460–467 (2007)Cite this article

Abstract

Schwannomas are benign tumors composed of dedifferentiated Schwann cells that form along peripheral nerves causing nerve compression often associated with pain and loss of function. Current surgical therapy involves total or subtotal surgical removal of the tumor, which may cause permanent nerve damage. In the present study, we explore an alternate means of therapy in which schwannomas are injected with a replication-conditional herpes simplex virus (HSV) vector to shrink the tumor through cell lysis during virus propagation. The oncolytic vector used, G47Δ, has deletions in HSV genes, which allow it to replicate selectively in dividing cells, sparing neurons. Two schwannoma cell lines were used to generate subcutaneous tumors in nude mice: HEI193, an immortalized human line previously established from an NF2 patient and NF2S-1, a newly generated spontaneous mouse line. Subcutaneous HEI193 tumors grew about ten times as fast as NF2S-1 tumors, and both regressed substantially following injection of G47Δ. Complete regression of HEI193 tumors was achieved in most animals, whereas all NF2S-1 tumors resumed growth within 2 weeks after vector injection. These studies provide a new schwannoma model for testing therapeutic strategies and demonstrate that oncolytic HSV vectors can be successfully used to shrink growing schwannomas.

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Acknowledgements

We thank Dr Mia MacCollin for her invaluable help in obtaining human schwannoma tissue, Dr Hung at the House Ear Institute for providing the human schwannoma cell line and Ms Suzanne McDavitt for skilled editorial assistance. This work was funded by the Department of the Army, US Army Medical Research and Material Command Award # DAMD17-00-1-0537 and W81XWH-04-1-0237. The Terrill Family and the Texas Neurofibromatosis Foundation.

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Author notes

  1. S M Messerli

    Present address: 5Current address: Woodshole Marine Biological Laboratories, 7 MBL St., Woodshole, MA 02543, USA.,

Authors and Affiliations

  1. Departments of Neurology and Radiology, Molecular Neurogenetics Unit, Massachusetts General Hospital, Charlestown, MA, USA

    S Prabhakar, S M Messerli & X O Breakefield

  2. Neuroscience Program, Harvard Medical School, Boston, MA, USA

    S Prabhakar, S M Messerli & X O Breakefield

  3. Molecular Neuro-Oncology Laboratory and Department of Pathology, Massachusetts General Hospital, Boston, MA, USA

    A O Stemmer-Rachamimov

  4. Department of Neurosurgery, Massachusetts General Hospital, Boston, MA, USA

    T-C Liu, S Rabkin & R Martuza

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  1. S Prabhakar
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Correspondence to X O Breakefield.

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Prabhakar, S., Messerli, S., Stemmer-Rachamimov, A. et al. Treatment of Implantable NF2 Schwannoma Tumor Models with Oncolytic Herpes Simplex Virus G47Δ. Cancer Gene Ther 14, 460–467 (2007). https://doi.org/10.1038/sj.cgt.7701037

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