Recent progress in and challenges in cellular therapy using NK cells for hematological malignancies.

NK cells have killing activity against leukemic cells and solid cancer cells that escape from T cell recognition because of the low expression level of HLA class I molecules. This characteristic feature of NK cell recognition of target cells in contrast to T cells provides a strategy to overcome tolerance in cancer and leukemia patients. A strong alloreactive NK cell-mediated anti-leukemia effect can be induced in haploidentical hematopoietic stem cell transplantation. Also, NK cells can be expanded by several methods for adoptive immunotherapy for hematological malignancies and other malignant diseases. We review the historical role of NK cells and recent approaches to enhance the functions of NK cells, including ex vivo expansion of autologous and allogenic NK cells, checkpoint receptor blockade, and the use of memory-like NK cells and CAR-NK cells, for treatment of hematological malignancies.