Therapeutic efficacy of G207 in a novel peripheral nerve sheath tumor model.
Nerve involvement poses a significant obstacle for the management of peripheral nervous system tumors, and nerve injury provides a frequent source of postoperative morbidity. The lack of suitable animal models for peripheral nerve tumors has impeded the development of alternative nerve-sparing therapies. To evaluate the effect of a multimutated replication-competent herpes simplex virus (G207) on the growth of peripheral nerve tumors and on nerve function, we developed a novel peripheral nerve sheath tumor model. Human neuroblastoma-derived cells injected into murine sciatic nerve consistently caused tumor development within the nerve sheath after 2 weeks followed by increasingly severe impairment of nerve function. Tumor treatment by a single intratumoral injection of G207 resulted in significant reduction of functional impairment, inhibition of tumor growth and prolonged survival. Direct injection of G207 viral particles into the healthy nerve sheath caused no obvious neurologic sequelae, whereas injections of wild-type virus resulted in uniform lethality. The results indicate that viral therapy might be considered as a safe alternative to surgical removal of tumors with peripheral nerve involvement.
Mashour
G A
GA
Department of Neurosurgery, Georgetown University, 3970 Reservoir Road NW, Washington, DC, 20007, USA.
Moulding
H D
HD
Chahlavi
A
A
Khan
G A
GA
Rabkin
S D
SD
Martuza
R L
RL
Driever
P H
PH
Kurtz
A
A
Chalavi
A
A
D000818:Animals; D003588:Cytopathogenic Effect, Viral; D004195:Disease Models, Animal; D005260:Female; D005822:Genetic Vectors / Q000235:genetics / Q000627:therapeutic use*; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009154:Mutation; D009368:Neoplasm Transplantation; D009374:Neoplasms, Experimental / Q000473:pathology / Q000628:therapy* / Q000821:virology; D018317:Nerve Sheath Neoplasms / Q000473:pathology / Q000628:therapy* / Q000821:virology; D009447:Neuroblastoma / Q000473:pathology / Q000628:therapy* / Q000821:virology; D012584:Sciatic Nerve / Q000473:pathology / Q000821:virology; D018139:Simplexvirus / Q000235:genetics / Q000254:growth & development*; D015996:Survival Rate; D016896:Treatment Outcome; D014407:Tumor Cells, Cultured; D014779:Virus Replication