¹Division of Hematology/Oncology, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, Ohio 45229, USA

Correspondence: Dr Timothy P Cripe, Hematology/Oncology, 3333 Burnet Ave., Cincinnati, OH 45229, USA. E-mail: timothy.cripe@cchmc.org

Received 11 May 2004; Published online 21 January 2005.

Abstract

Novel methods of local control for sarcomas are needed. We investigated the antitumor effect of two related herpes simplex virus (HSV) mutants, NV1020 and NV1066, on human rhabdomyosracoma cells and xenografts. Cell death correlated with virus replication and apoptosis in cultured cells and tumors. Complete regression was seen in all tumors <250 mm³ following a single injection, yet only half of tumors >250 mm³ showed a complete response. Fractionation of the virus dose into five injection sites did not increase transduction efficiency, transgene expression, or virus production, but did yield more widespread intratumoral distribution. Despite the same total dose of virus, improved control of large tumors was seen using fractionated injections as all large tumors (500–700 mm³) had durable, complete regression. Our data suggest that oncolytic HSVs may be useful for local control of bulky rhabdomyosarcoma tumors and that fractionated virus administration results in a more widespread virus infection and better tumor control. Therefore, strategies to maximize intratumoral virus distribution at initial delivery should be sought.