Combining Newcastle Disease Virus and Decitabine Enhances Leukemia Cell Death in Models of Murine Acute T-Cell Lymphocytic and Acute Myeloid Leukemias

Abstract

Acute T-cell leukemias (T-ALL) and acute myeloid leukemias (AML) are aggressive hematological cancers for which the standard of care has limited efficacy, with high rates of relapse. The DNA methyltransferase inhibitor decitabine (DCB) is an epigenetic modifier in clinical trials to treat leukemias, albeit with limited efficacy. Oncolytic viruses (OVs) preferentially replicate in and kill cancer cells but perform poorly against leukemias that are spread throughout normal tissues that can quench viral infections. We discovered that DCB and Newcastle disease virus (NDV), worked synergistically to reduce leukemia cell viability, in vitro, in murine T-ALL and AML models. Our data suggest treatment negatively regulated reactive oxygen/nitrogen species (RONS) production with differential effects between models at 12- to 48-hour timepoints. Furthermore, cytokine profiles did not correlate with the combination effect or RONS production. In conclusion, we have identified a synergistic combination therapy to potentially treat murine T-ALL and AML models.