Novel immunotherapy for AML using DNT cells (P4348)

Abstract Acute myeloid leukemia (AML) is the most common form of adult acute leukemia with very poor survival due to high relapse rates after chemotherapy. New therapeutic approaches that can effectively prevent relapse are needed. Human CD56-CD3+CD4-CD8- double negative T cells (DNTs) are a small subset of peripheral T cells. We have developed a protocol enabling ex vivo expansion of DNTs from both healthy donors and AML patients and showed recently that these DNTs have potent anti-leukemia activity in vitro. Here we further characterized the anti-leukemia properties of DNTs in vivo using a murine xenograft model. Following infusion into NSG mice, human DNTs proliferated and persisted for at least 14 days, and were detectable in spleen and bone marrow. DNTs did not kill normal bone marrow cells in vitro or in vivo. Unlike infusion of CD4+ or CD8+ T cells, DNT infusion did not cause graft-vs-host disease. Pre-treatment of AML blasts with allogeneic DNTs in vitro led to a 4-fold reduction in subsequent engraftment of CD45+CD33+ AML blasts in NSG mice. Further, infusion of DNTs expanded from an AML patient resulted in a 75% reduction in autologous CD33+ and CD34+ leukemia cell engraftment in NSG mice. These studies demonstrate that expansion of DNTs to therapeutic quantities is possible and that DNTs may be used as a novel immunotherapy to reduce AML burden by targeting primary leukemic blasts and potentially leukemic stem cells.