Abstract |
Oncolytic virotherapy is a promising novel therapy for glioblastoma that needs to be optimized before introduced to clinic. The targeting of conditionally replicating adenoviruses (CRAds) can be improved by relying on the tumor-tropic properties of neural stem cells (NSCs). Here, we report the characterization of an FDA approved NSC, HB1.F3-CD, as a cell carrier for CRAd-S-pk7, a glioma-tropic oncolytic adenovirus. We show that NSCs replicate and release infectious CRAd-S-pk7 progeny capable of lysing glioma cell lines. Moreover, ex-vivo-loaded NSCs, injected intracranially in nude mice bearing human glioma xenografts (i) retained their tumor tropism, (ii) continued to replicate CRAd-S-pk7 for more than a week after reaching the tumor site and (iii) successfully handed off CRAd-S-pk7 to glioma cells in vivo. Delivery via carrier cells reduced non-specific adenovirus distribution in the mouse brain. Moreover, we assessed biodistribution of loaded NSCs after intracranial injection in animal models semi-permissive to adenovirus replication, the Syrian hamster and cotton rat. NSCs did not migrate to distant organs and high levels of CRAd-S-pk7 DNA were observed only in the injected hemisphere. In conclusion, this optimized carrier system, with high efficiency of adenovirus delivery and minimal systemic toxicity, poses considerable advantages for anti- glioma oncolytic virotherapy.
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Authors | B Thaci, A U Ahmed, I V Ulasov, A L Tobias, Y Han, K S Aboody, M S Lesniak |
Journal | Cancer gene therapy
(Cancer Gene Ther)
Vol. 19
Issue 6
Pg. 431-42
(Jun 2012)
ISSN: 1476-5500 [Electronic] England |
PMID | 22555507
(Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
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Chemical References |
- Adenovirus E1A Proteins
- Recombinant Proteins
- Green Fluorescent Proteins
- Luciferases, Firefly
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Topics |
- Adenoviridae
(genetics, physiology)
- Adenovirus E1A Proteins
(biosynthesis, genetics)
- Animals
- Brain
(pathology, virology)
- Brain Neoplasms
(therapy)
- Cell Line
- Cell Survival
- Cricetinae
- Disease Models, Animal
- Glioma
(therapy)
- Green Fluorescent Proteins
(biosynthesis)
- Humans
- Luciferases, Firefly
(biosynthesis)
- Male
- Mice
- Mice, Nude
- Neoplasm Transplantation
- Neural Stem Cells
(transplantation)
- Oncolytic Virotherapy
(methods)
- Oncolytic Viruses
(genetics, physiology)
- Organisms, Genetically Modified
- Recombinant Proteins
(biosynthesis)
- Sigmodontinae
- Viral Load
- Virus Replication
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