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.

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 to assess its potential long-term toxicity.

authors

Lasner TM,Kesari S,Brown SM,Lee VM,Fraser NW,Trojanowski JQ

doi

10.1097/00005072-199612000-00010

subject

Has Abstract

pub_date

1996-12-01 00:00:00

pages

1259-69

issue

12

eissn

0022-3069

issn

1554-6578

journal_volume

55

pub_type

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