Targeting pediatric acute lymphoblastic leukemia with oncolytic measles

Background: Children with relapsed acute lymphoblastic leukemia (ALL) have a poor prognosis. Oncolytic viruses, i.e. attenuated measles (OMV), are effective against solid tumors. It was unknown whether OMV is efficacious in pediatric ALL.

Methods: OMV leukemolysis of pediatric primary B lineage ALL cells and xenografts (PDXs) was analysed by flow cytometry. OMV replication was examined as cytotoxic effect on indicator cells. Expression of OMV entry receptors and interferon response genes was determined by quantitative real-time PCR. In vivo, PDXs were transplanted into NOD/SCID mice. Following intravenous OMV injection, peripheral blood counts, histology and survival was monitored.

Results: OMV selectively replicates in, kills and spreads from pediatric ALL cells, irrespective of an intact transcriptional interferon response and the expression levels of the OMV entry receptors. OMV eradicated peripheral ALL and controlled CNS disease in PDXs in vivo.

Conclusion: A phase I study will be planed.