Potentiating oncolytic virus therapy for the treatment of Acute Myeloid Leukaemia

Acute myeloid leukaemia (AML) is a cancer of the blood and bone marrow and is characterised by the overproduction of immature myeloid cells. AML is most common in older adults, 65 being the median age of diagnosis, and is associated with a poor overall survival. Therefore, novel therapies are urgently required. Oncolytic viruses (OV) replicate preferentially within cancerous cells causing cell death and induce innate and adaptive anti-tumour immune responses. However, whilst OV have demonstrated promising results in solid malignancies, their potential for the treatment of AML remains poorly understood. Therefore, herein, we have investigated the efficacy of OVs against AML and developed a combination approach to boost OV efficacy. Using a panel of OV; reovirus, Maraba (MG1), coxsackievirus (CVA21) and herps simplex virus 1716 (HSV-1) we evaluated whether OV-induced pro-inflammatory cytokines or OV-direct oncolysis can kill AML cells, and examined whether apoptotic modulators (SMAC/ BH3 mimetics) could be used to increase OV efficacy.