Acute myeloid leukemia (AML) is a devastating cancer of the bone marrow resulting in progressive accumulation of leukemia cells and rapidly leads to bone marrow failure and death if not timely treated. In 2016, 20,000 new cases of AML and 10,000 disease-related deaths occurred in the United States alone. The median age at diagnosis is 67 years and the incidence of the disease increases with aging of the population. Estimated survival for AML patients diagnosed in the last 5 years in US is only 26.6%. Since 1969 only 5 drugs has been approved for treatment of AML. Therefore there is a clear unmet need for new and more active drugs. The current view is that AML treatment resistance or disease reoccurrence is due to the inability of current chemotherapy and/or molecular targeting drugs to eliminate the leukemia stem cells (LSC). These primitive malignant cells are capable of initiating and maintaining leukemia and are most resistant to current treatments. Here we propose to target and eliminate LSC by harnessing the immune system with newly synthesized bispecific antibodies and engineered T-cell cells aimed at IL1RAP, a protein that is preferentially expressed in LSC. Both these products are already in our hands and have a strong antileukemia activity and the ability to reduce LSC burden. Leveraging the infrastructure for drug development (including manufacturing facilities) already present at our Institution, we propose to complete preclinical, pharmacokinetic and pharmacodynamic studies and prepare for toxicology studies in order to move these products rapidly into the clinic.