Treatment of implantable NF2 schwannoma tumor models with oncolytic herpes simplex virus G47Δ

S. Prabhakar, S. M. Messerli, A. O. Stemmer-Rachamimov, T. C. Liu, S. Rabkin, R. Martuza, X. O. Breakefield

Research output: Contribution to journalArticlepeer-review

30 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)460-467
Number of pages8
JournalCancer Gene Therapy
Volume14
Issue number5
DOIs
StatePublished - May 2007

Keywords

  • HSV
  • Human schwannoma
  • Mouse schwannoma
  • Neurofibromatosis type 2
  • Oncolytic virus
  • Schwannoma cell line

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Cancer Research

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