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


METHODS
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.


CONCLUSIONS
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.
Division of Neurosurgery, Department of Surgery, Duke University Medical Center, Durham, North Carolina 27710, USA.
Hidenobu
H
Ochiai
Stephanie A
SA
Campbell
Gary E
GE
Archer
Tracy A
TA
Chewning
Eugenia
E
Dragunsky
Alexander
A
Ivanov
Matthias
M
Gromeier
John H
JH
Sampson
D000818:Animals; D019496:Cancer Vaccines / Q000008:administration & dosage* / Q000276:immunology; D045744:Cell Line, Tumor; D004305:Dose-Response Relationship, Drug; D005260:Female; D005909:Glioblastoma / Q000517:prevention & control*; D006801:Humans; D007278:Injections, Spinal; D008297:Male; D008565:Membrane Proteins / Q000235:genetics / Q000276:immunology; D008577:Meningeal Neoplasms / Q000517:prevention & control*; D051379:Mice; D008822:Mice, Transgenic; D017955:Poliovirus / Q000235:genetics / Q000276:immunology*; D011054:Poliovirus Vaccine, Inactivated / Q000008:administration & dosage / Q000276:immunology; D051381:Rats; D011923:Rats, Nude; D011991:Receptors, Virus / Q000235:genetics / Q000276:immunology; D011995:Recombination, Genetic; D016019:Survival Analysis; D023041:Xenograft Model Antitumor Assays / Q000379:methods*
D019496:Cancer Vaccines; D008565:Membrane Proteins; D011054:Poliovirus Vaccine, Inactivated; D011991:Receptors, Virus; C066100:poliovirus receptor