Ochiai Hidenobu, Campbell Stephanie A, Archer Gary E, Chewning Tracy A, Dragunsky Eugenia, Ivanov Alexander, Gromeier Matthias, Sampson John H
Division of Neurosurgery, Department of Surgery, Duke University Medical Center, Durham, North Carolina 27710, USA.
Clin Cancer Res. 2006 Feb 15;12(4):1349-54. doi: 10.1158/1078-0432.CCR-05-1595.
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.
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.
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.
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.
在多形性胶质母细胞瘤性脑膜炎的啮齿动物模型中评估溶瘤重组脊髓灰质炎病毒PVS - RIPO鞘内局部给药的毒性和抗肿瘤活性。
为评估毒性，将PVS - RIPO注入表达人脊髓灰质炎病毒受体CD155的转基因小鼠脊髓以及无肿瘤的裸鼠鞘内空间。为评估疗效，在裸鼠鞘内接种侵袭性人多形性胶质母细胞瘤异种移植物3天后，鞘内给予两种不同剂量的PVS - RIPO。
未发现临床或组织学毒性证据。在疗效研究中，中位生存期从紫外线灭活病毒治疗组的8.5天增加到接受1.0×10(7) 蚀斑形成单位（pfu）PVS - RIPO治疗的大鼠的15天，增加了174.47%（P < 0.0001）。接受1.0×10(9) pfu PVS - RIPO的组中位生存期也有类似增加（P < 0.0001）；然而，无统计学显著剂量反应关系（P = 0.345）。此外，低剂量PVS - RIPO治疗组10只大鼠中有1只、高剂量PVS - RIPO治疗组10只大鼠中有3只在肿瘤细胞接种后存活超过60天，尸检时无残留肿瘤证据。
这些结果表明，PVS - RIPO鞘内治疗可能对多形性胶质母细胞瘤患者的肿瘤性脑膜炎治疗有用，并为该领域的临床试验提供了理论依据。
