Grant: Project Grant

Blood cancer (leukemia) is a type of cancer that affects the blood and bone marrow; the disease develops when blood cells produced in the bone marrow grow out of control. In particular, acute myeloid leukemia (AML) is the most common human leukemia and is a major area of unmet medical need among blood cancers. In the past decade, major advancements have been made in identifying molecular and genetic sub-types to enable an understanding of the molecular pathways of AML pathogenesis, as well as potential therapeutic targets that have led to clinical trials and approved therapies. Despite this, AML treatment has not changed significantly over the past 40 years. Thus, the overall 5-year survival rate remains at 29%, with especially unfavorable prognosis for elderly patients. Resistance to frontline chemotherapy remains a major cause of treatment failure, highlighting the need for new therapies. This proposal aims to develop an innovative oncolytic virotherapy to effectively target AML patient cells that are resistant to current therapies. This pre-clinical study will evaluate the efficacy of novel anti-cancer oncolytic agents, alone or in combination with an immunotherapy, in targeting drug-resistant AML cells and their survival pathways in cell culture and in mouse models of human blood cancer. Interestingly, we have found that this proposed combination treatment strategy more effectively inhibits AML patient cell growth in culture than single agent treatment, which is very promising. We expect that this new treatment strategy will be more effective in eliminating critical blood cancer cells compared to traditional drugs and provide direct proof-of-concept for a subsequent clinical trial.