title: Neural stem cell-based cell carriers enhance therapeutic efficacy of an oncolytic adenovirus in an orthotopic mouse model of human glioblastoma.
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.
authors.affiliation: The Brain Tumor Center, The University of Chicago, Chicago, Illinois 60637, USA.
authors.forename: Atique U
authors.initials: AU
authors.lastname: Ahmed
authors.forename: Bart
authors.initials: B
authors.lastname: Thaci
authors.forename: Nikita G
authors.initials: NG
authors.lastname: Alexiades
authors.forename: Yu
authors.initials: Y
authors.lastname: Han
authors.forename: Shuo
authors.initials: S
authors.lastname: Qian
authors.forename: Feifei
authors.initials: F
authors.lastname: Liu
authors.forename: Irina V
authors.initials: IV
authors.lastname: Balyasnikova
authors.forename: Ilya Y
authors.initials: IY
authors.lastname: Ulasov
authors.forename: Karen S
authors.initials: KS
authors.lastname: Aboody
authors.forename: Maciej S
authors.initials: MS
authors.lastname: Lesniak
mesh_terms: D000256:Adenoviridae / Q000235:genetics / Q000502:physiology; D000818:Animals; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D015316:Genetic Therapy; D005822:Genetic Vectors / Q000235:genetics*; D005909:Glioblastoma / Q000628:therapy*; D008297:Male; D051379:Mice; D008819:Mice, Nude; D058953:Neural Stem Cells / Q000166:cytology* / Q000378:metabolism; D050130:Oncolytic Virotherapy / Q000379:methods*; D050504:Oncolytic Viruses / Q000235:genetics / Q000502:physiology; D014779:Virus Replication