Natural killer cells in leukemia and tumor therapy

Human natural killer (NK) cells represent 10-15% of lymphocytes in peripheral blood. As a part of the innate immune system they play a major role in first-line defense against infections and malignancies. NK cells show spontaneous cytotoxic activity against several leukemias and tumors with reduced human leukocyte antigen (HLA) class I expression in vitro and in mouse models. In particular following HLA-mismatched, haploidentical stem cell transplantation, significant NK cell-mediated antileukemic effects were shown in adult acute myeloic leukaemia, resulting in reduced relapse rates. These effects have been recently demonstrated also in pediatric acute leukemias. Infusions of donor NK cells during or after stem cell transplantation are currently being evaluated in clinical trials and promising preliminary results have been obtained. NK activity can be clearly increased by cytokine stimulation and by the use of appropriate antibodies against antigens on malignant cells. The feasibility and clinical efficacy of these options are also currently under evaluation in pediatric malignancies (e.g. acute leukemias and neuroblastomas).