Therapeutic efficacy of G207 in a novel peripheral nerve sheath tumor model

Nerve involvement poses a significant obstacle for the management of periph eral 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 thera pies. 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 sin gle intratumoral injection of G207 resulted in significant reduction of fun ctional impairment, inhibition of tumor growth and prolonged survival. Dire ct injection of G207 viral particles into the healthy nerve sheath caused n o obvious neurologic sequelae, whereas injections of wildtype virus resulte d in uniform lethality. The results indicate that viral therapy might be co nsidered as a safe alternative to surgical removal of tumors with periphera l nerve involvement. (C) 2001 Academic Press.