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.