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

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

Research output: Contribution to journalArticle

10 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)266-274
Number of pages9
JournalCancer Gene Therapy
Volume17
Issue number4
DOIs
StatePublished - Apr 1 2010

Fingerprint

Caspase 1
Investigational Therapies
Schwann Cells
Neurilemmoma
Enzymes
Neoplasms
Proteins
Nerve Fibers
Injections
Myelinated Nerve Fibers
Poisons
Spinal Ganglia
Deafness
Sciatic Nerve
Neuroblastoma
Peripheral Nerves
Heterografts
Paralysis
Cell Culture Techniques
Apoptosis

Keywords

  • Bioluminescence imaging
  • Caspase-1
  • Neurofibromatosis type 2
  • Tumors
  • Virus vectors

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Cancer Research

Cite this

Imaging and therapy of experimental schwannomas using HSV amplicon vector-encoding apoptotic protein under Schwann cell promoter. / Prabhakar, S.; Brenner, G. J.; Sung, B.; Messerli, Shanta; Mao, J.; Sena-Esteves, M.; Stemmer-Rachamimov, A.; Tannous, B.; Breakefield, X. O.

In: Cancer Gene Therapy, Vol. 17, No. 4, 01.04.2010, p. 266-274.

Research output: Contribution to journalArticle

Prabhakar, S, Brenner, GJ, Sung, B, Messerli, S, Mao, J, Sena-Esteves, M, Stemmer-Rachamimov, A, Tannous, B & Breakefield, XO 2010, 'Imaging and therapy of experimental schwannomas using HSV amplicon vector-encoding apoptotic protein under Schwann cell promoter', Cancer Gene Therapy, vol. 17, no. 4, pp. 266-274. https://doi.org/10.1038/cgt.2009.71
Prabhakar, S. ; Brenner, G. J. ; Sung, B. ; Messerli, Shanta ; Mao, J. ; Sena-Esteves, M. ; Stemmer-Rachamimov, A. ; Tannous, B. ; Breakefield, X. O. / Imaging and therapy of experimental schwannomas using HSV amplicon vector-encoding apoptotic protein under Schwann cell promoter. In: Cancer Gene Therapy. 2010 ; Vol. 17, No. 4. pp. 266-274.
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