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

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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.

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Acknowledgements

We thank Ms. Lingjiao Zhang for her expertise in the statistical analysis of our studies.

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Correspondence to M S Lesniak.

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Competing interests

AJA and KSA are share-holders, directors and officers of TheraBiologics, a clinical stage biopharmaceutical company focused on the development of stem cell-mediated cancer therapy. RAM is a director of TheraBiologics.

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Supplementary Information accompanies the paper on Cancer Gene Therapy website

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Morshed, R., Gutova, M., Juliano, J. et al. Analysis of glioblastoma tumor coverage by oncolytic virus-loaded neural stem cells using MRI-based tracking and histological reconstruction. Cancer Gene Ther 22, 55–61 (2015). https://doi.org/10.1038/cgt.2014.72

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