Efficacy of MV-NIS oncolytic measles virus against relapsed / refractory pediatric ALL and safety in the young and markedly immunocompromised primate

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Recently, the first oncolytic virus has been approved as a drug and the first complete remission of a disseminated cancer after virotherapy has been described in a patient receiving oncolytic measles virus (OMV). We have published that repeated i.v. injections of a laboratory strain of OMV control a moderate load of chemosensitive pediatric acute B-lineage ALL in mice. In the proposed project we aim to prove the efficacy of clinical-grade OMV, called MV-NIS, against pediatric relapsed / refractory ALL, including T ALL, under clinically relevant conditions, and to assess the safety of MV-NIS in young and markedly immunocompromised non-human primates and mice. Based on preliminary encouraging results we will investigate whether a single i.v. injection of MV-NIS suffices to cure mice with very high, widely disseminated loads of ALL xenografts from children that died of their refractory disease. We will explore whether high expression levels of proviral ADAR1 allow selection of patients whose ALL are likely to respond to MV-NIS. We will investigate toxicity of MV-NIS in novel models of very young and markedly immunocompromised non-human primates and mice. The results in these animal models will be important beyond oncolytic MV, as they also relate to the safety of measles vaccination in immunocompromised children. This project promises to meet the prerequisites for rapid clinical translation of this novel therapeutic approach to relapsed / refractory ALL.