New Investigator Research Grant Program

Our goal is to develop genetically engineered hematopoietic stem cell transplant (HSCT) for acute myeloid leukemia (AML), a difficult disease with few effective treatment options available. HSCT, also commonly known as a bone marrow transplant, is one of the few treatments that can achieve long-term cure for patients with AML, but many patients relapse even after HSCT. There is a critical need to develop better therapies that can improve survival for patients with AML. We propose to genetically engineer hematopoietic stem and progenitor cells (HSPCs) and give this to patients in combination with genetically modified T cells to increase the anti-leukemic effect of HSCT. Donor T cells will be modified to express a synthetic molecule called a chimeric antigen receptor (CAR) that enables specific targeting of leukemic cells, a strategy that has seen remarkable success in the treatment of B-cell acute lymphoblastic leukemia. In parallel, donor HSPCs will be modified to become resistant to CAR T cells, so that they can regenerate a healthy hematopoietic system that has been purged of AML. Importantly, this workflow ensures that we can take advantage of the established benefits of HSCT, while also creating additional opportunities for sustained disease remission using genetic engineering. Successful completion of the studies in this proposal will pave the way for implementation of a novel treatment strategy that can improve long-term survival for patients with AML.