Acute leukemia is the leading cause of death by cancer in children. Despite recent therapeutic advances, about 50% of children with acute leukemia refractory to chemotherapy still die from their disease. The only hope of cure for these children is hematopoietic stem cell transplantation because the stem cell generate an immune system able to kill leukemia cells. However, high-risk childhood acute myeloid and acute lymphoblastic leukemia are often resistant to immune killing and therefore leukemia relapses after transplantation. We have demonstrated that this resistance can be overcome by the stimulation of immune killer cells by plasmacytoid dendritic cells (pDC). We have showed that adoptive transfers of pDC control leukemia development in a model of human transplantation in mouse. We also developed a method to expand and differentiate pDC from human cord blood hematopoietic progenitors. This method allows for the clinical use of pDC in transplanted children. We named expanded pDC ThINKK for Therapeutic Inducers of Natural Killer cell Killing. We propose to translate these pre-clinical results into a novel Phase I clinical trial designed to maximize the effect of the immune system against leukemia and prevent relapse in transplanted children with high-risk leukemia. Our project is on the track for CTA filing in early 2023 and Phase I clinical trial opening in mid-2023.