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Targeted therapy for glioblastoma multiforme neoplastic meningitis with intrathecal delivery of an oncolytic recombinant poliovirus.

Hidenobu Ochiai, Stephanie A Campbell, Gary E Archer, Tracy A Chewning, Eugenia Dragunsky, Alexander Ivanov, Matthias Gromeier and John H Sampson
Hidenobu Ochiai
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Stephanie A Campbell
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Gary E Archer
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Tracy A Chewning
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Eugenia Dragunsky
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Alexander Ivanov
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Matthias Gromeier
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John H Sampson
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DOI: 10.1158/1078-0432.CCR-05-1595 Published February 2006
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Abstract

PURPOSE: The toxicity and antitumor activity of regional intrathecal delivery of an oncolytic recombinant poliovirus, PVS-RIPO, was evaluated in rodent models of glioblastoma multiforme neoplastic meningitis. EXPERIMENTAL DESIGN: To evaluate for toxicity, PVS-RIPO was administered into the spinal cord of transgenic mice that express the human poliovirus receptor, CD155, and into the intrathecal space of athymic rats without tumor. To evaluate efficacy, two different doses of PVS-RIPO were administered intrathecally 3 days after athymic rats were inoculated intrathecally with an aggressive human glioblastoma multiforme xenograft. RESULTS: No clinical or histologic evidence of toxicity was found. In efficacy studies, median survival was increased by 174.47% from 8.5 days in the group treated with UV light-inactivated virus to 15 days in the rats treated with 1.0 x 10(7) plaque-forming units (pfu) of PVS-RIPO (P < 0.0001). A similar increase in median survival was seen in the group receiving 1.0 x 10(9) pfu PVS-RIPO (P < 0.0001); however, there was no statistically significant dose-response relationship (P = 0.345). In addition, 1 of 10 rats in lower-dose PVS-RIPO-treated group and 3 of 10 rats in higher-dose PVS-RIPO-treated group survived >60 days after tumor cell inoculation and had no evidence of residual tumor at autopsy. CONCLUSION: These results suggest that intrathecal treatment with PVS-RIPO may be useful for treatment of neoplastic meningitis in patients with glioblastoma multiforme and provides a rationale for clinical trials in this area.

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Clinical Cancer Research: 12 (4)
February 2006
Volume 12, Issue 4
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Targeted therapy for glioblastoma multiforme neoplastic meningitis with intrathecal delivery of an oncolytic recombinant poliovirus.
Hidenobu Ochiai, Stephanie A Campbell, Gary E Archer, Tracy A Chewning, Eugenia Dragunsky, Alexander Ivanov, Matthias Gromeier and John H Sampson
Clin Cancer Res February 15 2006 (12) (4) 1349-1354; DOI: 10.1158/1078-0432.CCR-05-1595

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Targeted therapy for glioblastoma multiforme neoplastic meningitis with intrathecal delivery of an oncolytic recombinant poliovirus.
Hidenobu Ochiai, Stephanie A Campbell, Gary E Archer, Tracy A Chewning, Eugenia Dragunsky, Alexander Ivanov, Matthias Gromeier and John H Sampson
Clin Cancer Res February 15 2006 (12) (4) 1349-1354; DOI: 10.1158/1078-0432.CCR-05-1595
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Clinical Cancer Research
eISSN: 1557-3265
ISSN: 1078-0432

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