Serotype-Specific Killing of Large Cell Carcinoma Cells by ReovirusReportar como inadecuado


Serotype-Specific Killing of Large Cell Carcinoma Cells by Reovirus


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Department of Microbiology and Immunology and Center for Microbial Pathogenesis and Host Inflammatory Response, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA





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Academic Editor: Andrew Mehle

Abstract Reovirus is under development as a therapeutic for numerous types of cancer. In contrast to other oncolytic viruses, the safety and efficacy of reovirus have not been improved through genetic manipulation. Here, we tested the oncolytic capacity of recombinant strains rs of prototype reovirus laboratory strains T1L and T3D rsT1L and rsT3D, respectively in a panel of non-small cell lung cancer NSCLC cell lines. We found that rsT1L was markedly more cytolytic than rsT3D in the large cell carcinoma cell lines tested, whereas killing of adenocarcinoma cell lines was comparable between rsT1L and rsT3D. Importantly, non-recombinant T1L and T3D phenocopied the kinetics and magnitude of cell death induced by recombinant strains. We identified gene segments L2, L3, and M1 as viral determinants of strain-specific differences cell killing of the large cell carcinoma cell lines. Together, these results indicate that recombinant reoviruses recapitulate the cell killing properties of non-recombinant, tissue culture-passaged strains. These studies provide a baseline for the use of reverse genetics with the specific objective of engineering more effective reovirus oncolytics. This work raises the possibility that type 1 reoviruses may have the capacity to serve as more effective oncolytics than type 3 reoviruses in some tumor types. View Full-Text

Keywords: reovirus; oncolysis; lung cancer; reverse genetics reovirus; oncolysis; lung cancer; reverse genetics





Autor: Emily J. Simon, Morgan A. Howells, Johnasha D. Stuart and Karl W. Boehme *

Fuente: http://mdpi.com/



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