Imaging and therapy of experimental schwannomas using HSV amplicon vector-encoding apoptotic protein under Schwann cell promoter.
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.
Prabhakar
S
S
Neuroscience Center, Massachusetts General Hospital, Boston, MA 02129, USA.
Brenner
G J
GJ
Sung
B
B
Messerli
S M
SM
Mao
J
J
Sena-Esteves
M
M
Stemmer-Rachamimov
A
A
Tannous
B
B
Breakefield
X O
XO
D000818:Animals; D020170:Caspase 1 / Q000235:genetics*; D003952:Diagnostic Imaging; D005453:Fluorescence; D005455:Fluorescent Antibody Technique; D018014:Gene Transfer Techniques; D015316:Genetic Therapy; D005822:Genetic Vectors / Q000627:therapeutic use; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D006561:Herpes Simplex / Q000378:metabolism / Q000473:pathology / Q000628:therapy; D006801:Humans; D049449:Luminescence; D051379:Mice; D008819:Mice, Nude; D009442:Neurilemmoma / Q000378:metabolism / Q000473:pathology* / Q000628:therapy*; D050130:Oncolytic Virotherapy; D011401:Promoter Regions, Genetic / Q000235:genetics*; D012583:Schwann Cells / Q000378:metabolism / Q000473:pathology / Q000821:virology; D018139:Simplexvirus / Q000235:genetics*; D014161:Transduction, Genetic
C485184:enhanced green fluorescent protein; D049452:Green Fluorescent Proteins; D020170:Caspase 1