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Imaging and therapy of experimental schwannomas using HSV amplicon vector-encoding apoptotic protein under Schwann cell promoter

Cancer Gene Therapy volume 17, pages 266–274 (2010)Cite this article

Abstract

Schwannomas are benign tumors forming along peripheral nerves that can cause deafness, pain and paralysis. Current treatment involves surgical resection, which can damage associated nerves. To achieve tumor regression without damage to nerve fibers, we generated an HSV amplicon vector in which the apoptosis-inducing enzyme, caspase-1 (ICE), was placed under the Schwann cell-specific P0 promoter. Infection of schwannoma, neuroblastoma and fibroblastic cells in culture with ICE under the P0 promoter showed selective toxicity to schwannoma cells, while ICE under a constitutive promoter was toxic to all cell types. After direct intratumoral injection of the P0-ICE amplicon vector, we achieved marked regression of schwannoma tumors in an experimental xenograft mouse model. Injection of this amplicon vector into the sciatic nerve produced no apparent injury to the associated dorsal root ganglia neurons or myelinated nerve fibers. The P0-ICE amplicon vector provides a potential means of ‘knifeless resection’ of schwannoma tumors by injection of the vector into the tumor with low risk of damage to associated nerve fibers.

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Abbreviations

CCD:

charged-coupling device

CMV:

cytomegalovirus

CNS:

central nervous system

CV:

conduction velocity

DRG:

dorsal root ganglia

EGFR:

epidermal growth factor receptor

FBS:

fetal bovine serum

Fluc:

firefly luciferase

GFP:

green fluorescent protein

HSV:

herpes simplex virus type 1

ICE:

caspase-1

MCS:

multiple cloning site

MOI:

multiplicity of infection (tu per cell)

NF2:

neurofibromatosis type 2

PBS:

phosphate buffered saline

PNS:

peripheral nervous system

tu:

transducing units

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Acknowledgements

We thank Ms. Suzanne McDavitt for skilled editorial assistance. This work was supported by grants from NINDS NS024279, Department of the Army, US Army Research Medical Research and Material Command Award W81XWH-04-1-0237, the P41 RR001395 NCRR grant, the Terrill Family and Texas Neurofibromatosis Foundation.

Author information

Author notes

  1. S M Messerli

    Present address: 8Current address: Biocurrents Research Center, Marine Biological Laboratory, Woods Hole, MA 02543 USA.,

Authors and Affiliations

  1. Neuroscience Center, Massachusetts General Hospital, Boston, MA, USA

    S Prabhakar, G J Brenner, B Sung, S M Messerli, J Mao, M Sena-Esteves, A Stemmer-Rachamimov, B Tannous & X O Breakefield

  2. Department of Neurology, Massachusetts General Hospital, Boston, MA, USA

    S Prabhakar, S M Messerli, M Sena-Esteves, B Tannous & X O Breakefield

  3. Program in Neuroscience, Harvard Medical School, Boston, MA, USA

    S Prabhakar, S M Messerli & M Sena-Esteves

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

    G J Brenner

  5. Department of Anesthesia and Critical Care, Pain Research Group, Massachusetts General Hospital, Boston, MA, USA

    B Sung & J Mao

  6. Department of Pathology, Massachusetts General Hospital, Boston, MA, USA

    A Stemmer-Rachamimov & X O Breakefield

  7. Department of Radiology, Center for Molecular Imaging Research, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA

    B Tannous & X O Breakefield

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Correspondence to X O Breakefield.

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Prabhakar, S., Brenner, G., Sung, B. et al. Imaging and therapy of experimental schwannomas using HSV amplicon vector-encoding apoptotic protein under Schwann cell promoter. Cancer Gene Ther 17, 266–274 (2010). https://doi.org/10.1038/cgt.2009.71

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