Neural stem cell-based cell carriers enhance therapeutic efficacy of an oncolytic adenovirus in an orthotopic mouse model of human glioblastoma

Atique U. Ahmed, Bart Thaci, Nikita G. Alexiades, Yu Han, Shuo Qian, Feifei Liu, Irina V. Balyasnikova, Ilya Y. Ulasov, Karen S. Aboody, Mac Iej S Lesniak*

*Corresponding author for this work

Research output: Contribution to journalArticle

68 Citations (Scopus)

Abstract

The potential utility of oncolytic adenoviruses as anticancer agents is significantly hampered by the inability of the currently available viral vectors to effectively target micrometastatic tumor burden. Neural stem cells (NSCs) have the ability to function as cell carriers for targeted delivery of an oncolytic adenovirus because of their inherent tumor-tropic migratory ability. We have previously reported that in vivo delivery of CRAd-S-pk7, a glioma-restricted oncolytic adenovirus, can enhance the survival of animals with experimental glioma. In this study, we show that intratumoral delivery of NSCs loaded with the CRAD-S-pk7 in an orthotopic xenograft model of human glioma is able to not only inhibit tumor growth but more importantly to increase median survival by ∼50% versus animals treated with CRAd-S-pk7 alone (P = 0.0007). We also report that oncolytic virus infection upregulates different chemoattractant receptors and significantly enhances migratory capacity of NSCs both in vitro and in vivo. Our data further suggest that NSC-based carriers have the potential to improve the clinical efficacy of antiglioma virotherapy by not only protecting therapeutic virus from the host immune system, but also amplifying the therapeutic payload selectively at tumor sites.

Original languageEnglish (US)
Pages (from-to)1714-1726
Number of pages13
JournalMolecular Therapy
Volume19
Issue number9
DOIs
StatePublished - Jan 1 2011

Fingerprint

Neural Stem Cells
Glioblastoma
Adenoviridae
Glioma
Oncolytic Viruses
Formyl Peptide Receptor
Neoplasms
Virus Diseases
Therapeutics
Tumor Burden
Heterografts
Antineoplastic Agents
Immune System
Up-Regulation
Viruses
Survival
Growth

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Genetics
  • Pharmacology
  • Drug Discovery

Cite this

Ahmed, Atique U. ; Thaci, Bart ; Alexiades, Nikita G. ; Han, Yu ; Qian, Shuo ; Liu, Feifei ; Balyasnikova, Irina V. ; Ulasov, Ilya Y. ; Aboody, Karen S. ; Lesniak, Mac Iej S. / Neural stem cell-based cell carriers enhance therapeutic efficacy of an oncolytic adenovirus in an orthotopic mouse model of human glioblastoma. In: Molecular Therapy. 2011 ; Vol. 19, No. 9. pp. 1714-1726.
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abstract = "The potential utility of oncolytic adenoviruses as anticancer agents is significantly hampered by the inability of the currently available viral vectors to effectively target micrometastatic tumor burden. Neural stem cells (NSCs) have the ability to function as cell carriers for targeted delivery of an oncolytic adenovirus because of their inherent tumor-tropic migratory ability. We have previously reported that in vivo delivery of CRAd-S-pk7, a glioma-restricted oncolytic adenovirus, can enhance the survival of animals with experimental glioma. In this study, we show that intratumoral delivery of NSCs loaded with the CRAD-S-pk7 in an orthotopic xenograft model of human glioma is able to not only inhibit tumor growth but more importantly to increase median survival by ∼50{\%} versus animals treated with CRAd-S-pk7 alone (P = 0.0007). We also report that oncolytic virus infection upregulates different chemoattractant receptors and significantly enhances migratory capacity of NSCs both in vitro and in vivo. Our data further suggest that NSC-based carriers have the potential to improve the clinical efficacy of antiglioma virotherapy by not only protecting therapeutic virus from the host immune system, but also amplifying the therapeutic payload selectively at tumor sites.",
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Neural stem cell-based cell carriers enhance therapeutic efficacy of an oncolytic adenovirus in an orthotopic mouse model of human glioblastoma. / Ahmed, Atique U.; Thaci, Bart; Alexiades, Nikita G.; Han, Yu; Qian, Shuo; Liu, Feifei; Balyasnikova, Irina V.; Ulasov, Ilya Y.; Aboody, Karen S.; Lesniak, Mac Iej S.

In: Molecular Therapy, Vol. 19, No. 9, 01.01.2011, p. 1714-1726.

Research output: Contribution to journalArticle

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