Cytotoxicity and clinical application of activated NK cells.

We have shown that the patients with myelogenous leukemia display several defects in the NK cell lytic mechanism. However, this cytotoxic defect could be corrected after culture of effector cells from these patients with IL-2. The cytotoxic potential of IL-2-activated killer cells could be further augmented by treatment with OKT3 monoclonal antibody. Interleukin-2-activated lymphocytes were effective in killing not only a variety of tumor cell lines, but also autologous leukemic cells. Moreover, these cells were not stationary, but proliferated actively in culture with IL-2. Characterization studies, using the monoclonal antibodies against NK cell (CD16 and NKH1/Leu-19) or T-cell (CD3 and CD5) surface molecules showed that the antileukemia-directed cytotoxic cells were NK cells and not T-cells. In contrast, the T-cells (and not NK cells) exhibited an ability to down-regulate clonogenic activity of hematopoietic progenitors and to inhibit proliferation of bone marrow cells. Our data suggest that adoptive therapy with highly-enriched IL-2-activated NK cells may result in more powerful anti-leukemia effect. Alternatively, activated NK cells may be effective in eradication of leukemic cells from bone marrow for autologous bone marrow transplantation purposes.