Recent advances in chimeric antigen receptor natural killer cell therapy for overcoming intractable hematological malignancies.

Natural killer (NK) cells have a potent cytotoxic activity against leukemia and lymphoma without recognition of human leukocyte antigen (HLA) molecules. Chimeric antigen receptor-engineered NK cells (CAR-NK cells) can be produced from the NK92 cell line, peripheral blood, cord blood, and induced pluripotent stem cells for immunotherapy of malignant tumor cells. Recently, the safety and efficacy of HLA-mismatched allogeneic cord blood-derived CD19 CAR-NK cell therapy for CD19-positive hematological malignancies have been reported. However, the durability of clinical effects has not been clarified. The characteristics of CAR-NK cells with a strong antileukemia/lymphoma effect and better proliferative capacity without severe adverse effects may be promising for overcoming intractable hematological malignancies as an off-the-shelf allogeneic cellular therapy.