Efficient delivery of oncolytic enterovirus by carrier cell line NK-92

Many members of the enterovirus family are considered as promising oncolytic agents; however, their systemic administration is largely inefficient due to the rapid neutralization of the virus in the circulation and the barrier functions of the endothelium. We aimed to evaluate natural killer cells a...

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Bibliographic Details
Published in:Molecular therapy. Oncolytics 2021-06, Vol.21, p.110-118
Main Authors: Podshivalova, Elizaveta Sergeevna, Semkina, Alevtina Sergeevna, Kravchenko, Dmitry Sergeevich, Frolova, Elena Ivanovna, Chumakov, Stepan Petrovich
Format: Article
Language:English
Subjects:
carrier cells
coxsackievirus
CVA7
glioblastoma multiforme
NK-92
oncolytic enteroviruses
Original
viral oncolysis
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Summary:Many members of the enterovirus family are considered as promising oncolytic agents; however, their systemic administration is largely inefficient due to the rapid neutralization of the virus in the circulation and the barrier functions of the endothelium. We aimed to evaluate natural killer cells as carriers for the delivery of oncolytic enteroviruses, which would combine the effects of cell immunotherapy with virotherapy. We tested four strains of nonpathogenic enteroviruses against the glioblastoma cell line panel and evaluated the produced infectious titers. Next, we explored whether these virus strains could be delivered to the tumor by natural killer cell line NK-92, which is being actively evaluated as a clinically acceptable therapeutic. Several strains of enteroviruses demonstrated oncolytic properties, but only coxsackievirus A7 (CVA7) could replicate in NK-92 cells efficiently. We compared the delivery efficiency of CVA7 in vivo, using NK-92 cells and direct intravenous administration, and found significant advantages of cell delivery even after a single injection. This suggests that the NK-92 cell line can be utilized as a vehicle for the delivery of the oncolytic strain of CVA7, which would improve the clinical potential of this viral oncolytic for the treatment of glioblastoma multiforme and other forms of cancer. [Display omitted] Natural killer cell line NK-92 is a safe and clinically approved therapeutic instrument. This study shows that NK-92 cells could be utilized as delivery carriers for oncolytic enterovirus coxsackie A7. NK-92-mediated virus delivery required lower virus dosage than direct intravenous administration of the virus to treat glioblastoma tumor xenografts.
ISSN:2372-7705
2372-7705
DOI:10.1016/j.omto.2021.03.013