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Cancer Gene Ther. 2015 Jan;22(1):55-61. doi: 10.1038/cgt.2014.72. Epub 2014 Dec 19.

Analysis of glioblastoma tumor coverage by oncolytic virus-loaded neural stem cells using MRI-based tracking and histological reconstruction.

Author information

1
The Brain Tumor Center, Pritzker School of Medicine, The University of Chicago, Chicago, IL, USA.
2
Department of Neuroscience, City of Hope National Medical Center, Beckman Research Institute, Duarte, CA, USA.
3
Northwestern Brain Tumor Institute, Robert H. Lurie Cancer Center, Chicago, IL, USA.
4
1] Department of Neuroscience, City of Hope National Medical Center, Beckman Research Institute, Duarte, CA, USA [2] Division of Neurosurgery, City of Hope National Medical Center, Beckman Research Institute, Duarte, CA, USA [3] Department of Radiology, Children's Hospital of Los Angeles, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
5
Department of Radiology, Children's Hospital of Los Angeles, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
6
1] Department of Neuroscience, City of Hope National Medical Center, Beckman Research Institute, Duarte, CA, USA [2] Division of Neurosurgery, City of Hope National Medical Center, Beckman Research Institute, Duarte, CA, USA.

Abstract

In preclinical studies, neural stem cell (NSC)-based delivery of oncolytic virus has shown great promise in the treatment of malignant glioma. Ensuring the success of this therapy will require critical evaluation of the spatial distribution of virus after NSC transplantation. In this study, the patient-derived GBM43 human glioma line was established in the brain of athymic nude mice, followed by the administration of NSCs loaded with conditionally replicating oncolytic adenovirus (NSC-CRAd-S-pk7). We determined the tumor coverage potential of oncolytic adenovirus by examining NSC distribution using magnetic resonance (MR) imaging and by three-dimensional reconstruction from ex vivo tissue specimens. We demonstrate that unmodified NSCs and NSC-CRAd-S-pk7 exhibit a similar distribution pattern with most prominent localization occurring at the tumor margins. We were further able to visualize the accumulation of these cells at tumor sites via T2-weighted MR imaging as well as the spread of viral particles using immunofluorescence. Our analyses reveal that a single administration of oncolytic virus-loaded NSCs allows for up to 31% coverage of intracranial tumors. Such results provide valuable insights into the therapeutic potential of this novel viral delivery platform.

PMID:
25525033
PMCID:
PMC4293243
DOI:
10.1038/cgt.2014.72
[Indexed for MEDLINE]
Free PMC Article

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