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Non-invasive in vivo monitoring of trackable viruses expressing soluble marker peptides

Abstract

Noninvasive methods are needed to study the kinetic properties of viruses in living organisms. Oncolytic viruses are used increasingly for cancer therapy but there is currently no satisfactory way to measure efficiency of tumor transduction, changing levels of viral gene expression or the timing of virus elimination. We therefore generated trackable oncolytic measles viruses expressing inert (nonimmunogenic, nonfunctional and accurately measurable) soluble marker peptides. The marker peptides did not compromise virus replication. Ex vivo and in vivo kinetics of the trackable viruses could be easily followed by measuring the concentrations of virally encoded marker peptides in culture supernatant or in serum. When mice bearing human tumor xenografts were challenged with the trackable viruses, distinct kinetic profiles of marker-gene expression could be correlated with distinct therapeutic outcomes. Oncolytic viruses expressing inert soluble marker polypeptides should greatly facilitate the rational development of effective, individually tailored cancer virotherapy.

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Figure 1: Ex vivo characterization of the recombinant viruses.
Figure 2: Monitoring the in vivo expression profile of trackable MV-Edms.
Figure 3: Kinetic profiles of marker-gene expression correlate with response to intravenous MV-shCEA therapy in different tumor xenografts.
Figure 4: Relative levels of viral gene expression in human xenografts in immunocompromised mice injected intravenously with MV-shCEA can be evaluated by determining serum CEA concentrations.

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Acknowledgements

We thank R. Cattaneo for reagents (293-3-46, p(+)MV-eGFP, CD46 transgenic mice) and advice on the measles virus rescue system; A. Pèlegrin and N. Eberhardt, respectively, for the CEA and βhCG cDNAs; M. Federspiel and R. Cattaneo for critical reading of the manuscript; and J. Ludvigson for help with the transgenic mice. This work was supported by the Harold Siebens Foundation, the George Eisenberg Foundation, and NIH grant PO1 HL 66958-1 A1.

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Peng, KW., Facteau, S., Wegman, T. et al. Non-invasive in vivo monitoring of trackable viruses expressing soluble marker peptides. Nat Med 8, 527–531 (2002). https://doi.org/10.1038/nm0502-527

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