Treatment of Schwannomas with an oncolytic recombinant herpes simplex virus in murine models of neurofibromatosis type 2

Shanta Messerli, Shilpa Prabhakar, Yi Tang, Umar Mahmood, Ralph Weissleder, Rodrick Bronson, Robert Martuza, Samuel Rabkin, Xandra O. Breakefield

Research output: Contribution to journalArticle

28 Citations (Scopus)

Abstract

Gene therapy for schwannomas was evaluated in two mouse models of neurofibromatosis type 2 (NF2): (1) a transgenic model in which mice express a dominant mutant form of merlin and spontaneously develop schwannomas, and (2) a xenograft model in which human schwannoma tissue is implanted subcutaneously into immune-compromised mice. In both models, schwannoma volumes were monitored by magnetic resonance imaging (MRI) and showed strong gadolinium enhancement typical of these tumors in humans. Both types of tumor were positive for the Schwann cell marker S100, and highly infectable with herpes simplex virus (HSV) vectors. Schwannomas were injected with an oncolytic HSV-1 recombinant virus vector, G47Δ, which has deletions in genes for ribonucleotide reductase (ICP6), γ34.5, and ICP47. In the NF2 transgenic model, schwannomas were reduced by more than half their original size by 10 days after infection. In the case of subcutaneous schwannoma xenografts, reduction in size after infection occurred more slowly, with a mean reduction of one-third by 42 days after treatment. Schwannomas injected with control vehicles continued to grow slowly over time in both schwannoma models. These studies demonstrate the ability of an oncolytic recombinant HSV vector to reduce the volume of schwannoma tumors in NF2 tumor models in mice and extend the possible therapeutic applications of oncolytic vectors for benign tumors to reduce mass while minimizing nerve damage.

Original languageEnglish (US)
Pages (from-to)20-30
Number of pages11
JournalHuman Gene Therapy
Volume17
Issue number1
DOIs
StatePublished - Jan 1 2006

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Neurofibromatosis 2
Neurilemmoma
Simplexvirus
Therapeutics
Heterografts
Neoplasms
Neurofibromin 2
Oncolytic Viruses
Ribonucleotide Reductases
Neurofibromatosis 1
Schwann Cells
Gene Deletion
Gadolinium
Human Herpesvirus 1
Infection
Tumor Burden
Genetic Therapy
Magnetic Resonance Imaging

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Genetics

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Treatment of Schwannomas with an oncolytic recombinant herpes simplex virus in murine models of neurofibromatosis type 2. / Messerli, Shanta; Prabhakar, Shilpa; Tang, Yi; Mahmood, Umar; Weissleder, Ralph; Bronson, Rodrick; Martuza, Robert; Rabkin, Samuel; Breakefield, Xandra O.

In: Human Gene Therapy, Vol. 17, No. 1, 01.01.2006, p. 20-30.

Research output: Contribution to journalArticle

Messerli, S, Prabhakar, S, Tang, Y, Mahmood, U, Weissleder, R, Bronson, R, Martuza, R, Rabkin, S & Breakefield, XO 2006, 'Treatment of Schwannomas with an oncolytic recombinant herpes simplex virus in murine models of neurofibromatosis type 2', Human Gene Therapy, vol. 17, no. 1, pp. 20-30. https://doi.org/10.1089/hum.2006.17.20
Messerli, Shanta ; Prabhakar, Shilpa ; Tang, Yi ; Mahmood, Umar ; Weissleder, Ralph ; Bronson, Rodrick ; Martuza, Robert ; Rabkin, Samuel ; Breakefield, Xandra O. / Treatment of Schwannomas with an oncolytic recombinant herpes simplex virus in murine models of neurofibromatosis type 2. In: Human Gene Therapy. 2006 ; Vol. 17, No. 1. pp. 20-30.
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