Treatment of Experimental Intracranial Murine Melanoma with a Neuroattenuated Herpes Simplex Virus 1 Mutant

Bruce P. Randazzo, Santosh Kesari, Richard M. Gesser, David Alsop, John C. Ford, S. Moira Brown, Alasdair Maclean, Nigel W. Fraser

Research output: Contribution to journalArticlepeer-review

94 Scopus citations

Abstract

Brain metastases occur commonly in the setting of a variety of human cancers. At present, such cases are invariably fatal and highlight a need for research on new therapies. We have developed a mouse brain tumor model utilizing the Harding-Passey melanoma cell line injected intracranially into C57BI/6 mice. Tumors develop in 100% of the mice and can be detected by magnetic resonance imaging as early as 5 days post cell injection. Death from tumor progression occurs between 12 and 16 days post cell injection. Stereotactic injection of the neuroattenuated HSV-1 strain 1716 into brain tumors 5 or 10 days postinjection of the melanoma cells results in a statistically significant increase in the time to development of neurological symptoms and in complete tumor regression and the long-term survival of some treated animals. Moreover, viral titration studies and immunohistochemistry suggest that replication of this virus is restricted to tumor cells and does not occur in the surrounding brain tissue. These results suggest that HSV-1 mutant 1716 shows particular promise for use as a therapeutic agent for the treatment of brain tumors.

Original languageEnglish (US)
Article number71382
Pages (from-to)94-101
Number of pages8
JournalVirology
Volume211
Issue number1
DOIs
StatePublished - Aug 1 1995
Externally publishedYes

ASJC Scopus subject areas

  • Virology

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