Therapy of a murine model of pediatric brain tumors using a herpes simplex virus type-1 ICP34.5 mutant and demonstration of viral replication within the CNS

Journal of Neuropathology and Experimental Neurology
T M LasnerJ Q Trojanowski

Abstract

To develop improved therapies for medulloblastoma, we studied the ability of a neuroattenuated HSV-1 ICP34.5 mutant (variant-1716) to replicate within and destory an authentic medulloblastoma cell line known as Med 283 (D283) using immunohistochemistry, in situ hybridization, and viral titrations. In vitro studies showed that variant-1716 replicates in and destroys monolayers of D283 cells with kinetics similar to wild-type strain 17+. When D283 tumor-bearing animals were treated with variant-1716 injected directly into the tumor, there was a statistically significant increase in survival (p < .02) compared to mock-treated tumor-bearing mice. Additionally, several novel observations emerged from this study. Most importantly, we demonstrated focal acute viral replication within murine brain cells, a finding not previously reported with HSV-1 ICP-34.5 variants. Further, the brains of tumor-bearing animals treated with variant-1716 demonstrated persistent viral replication within tumors for several weeks. Thus, we conclude that variant-1716 causes a statistically significant increase in survival of experimental medulloblastomas, but further analysis of the replication of HSV-1 ICP34.5 mutants within the mammalian CNS is necessary ...Continue Reading

Citations

Apr 16, 2009·Molecular Therapy : the Journal of the American Society of Gene Therapy·Gregory K FriedmanG Yancey Gillespie
Mar 21, 2012·Pediatric Research·Gregory K FriedmanG Yancey Gillespie
Mar 2, 2012·Journal of Virology·James M MarkertRichard J Whitley
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