Recent advances in cell therapy for AML/MDS.

Cellular immunotherapy has substantially changed the treatment of B-cell leukemias, lymphomas, and multiple myeloma. The success of chimeric antigen receptor (CAR)-T cell therapy in these diseases has been supported by suitable target antigens, including CD19 in B-cell malignancies and B-cell maturation antigen in multiple myeloma. In contrast, comparable progress has not yet been achieved in acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS), in part because an optimal target with clinically manageable on-target effects on normal cells has not been identified. Nevertheless, identification of an appropriate target could enable major therapeutic advances with CAR-T cell therapy in myeloid malignancies. To further harness the potential of cellular immunotherapy in AML/MDS, a multifaceted approach may be required. In parallel with CAR-T cell development, CAR-NK cells, T-cell receptor-engineered T cells, NK cells and other innate immune approaches are actively explored, while allogeneic hematopoietic stem cell transplantation remains an established form of cellular immunotherapy for AML/MDS. These approaches may be developed in parallel and, where appropriate, integrated with molecularly targeted and other pharmacologic therapies. This issue of Progress in Hematology reviews these emerging directions and their potential to expand cellular therapy for AML/MDS.