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Widespread intratumoral virus distribution with fractionated injection enables local control of large human rhabdomyosarcoma xenografts by oncolytic herpes simplex viruses

Cancer Gene Therapy volume 12, pages 407–416 (2005)Cite this article

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.

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Acknowledgements

We thank Frank Tufaro, Brian Horsburgh, and MediGene, Inc. for providing virus; James Wells and Marie-Dominique Filippi for help with fluorescence microscopy, Michelle Sudheimer and Rebecca Haas for technical assistance; and Nancy Sawtell for rabbit skin cells and advice. This work was supported by grants from the Foundation for the Children's Oncology Group (Chair's Developmental Fund), the Cincinnati Children's Hospital Translational Research Initiative, TeeOffAgainstCancer.org, an American Medical Association Foundation Seed Grant to YYM, and by the American Cancer Society Research Scholar Grant #RSG-02-254-01-MGO to TPC.

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

    Mark A Currier, Lisa C Adams, Yonatan Y Mahller & Timothy P Cripe

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Correspondence to Timothy P Cripe.

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Currier, M., Adams, L., Mahller, Y. et al. Widespread intratumoral virus distribution with fractionated injection enables local control of large human rhabdomyosarcoma xenografts by oncolytic herpes simplex viruses. Cancer Gene Ther 12, 407–416 (2005). https://doi.org/10.1038/sj.cgt.7700799

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