Natural killer (NK) cells play an important role as effector cells in innate immunity. Through specific inhibitory receptors that recognize major histocompatibility complex (MHC) antigens, these cells are able to react specifically to transformed cells that have either lost or mismatched expression of MHC.¹ The proliferation of NK cells can be stimulated by cytokines such as interleukin (IL)-2 and IL-15 and the cytolytic functions of NK cells can be enhanced by IL-2, IL-12 and IL-15.^2,3 Previous studies have suggested that these activated NK cells can play an important role in the elimination of acute myeloid leukemia cells in vivo but little activity has been demonstrated against acute lymphocytic leukemia (ALL) cells.⁴ In an extensive series of studies described in this issue, Torelli et al. (page 785) developed methods for ex vivo expansion of human NK cells from pediatric and adult patients with ALL in complete remission after completion of conventional therapy. Ex vivo expanded NK cells maintained normal cytolytic functions and were active against autologous leukemia cells cryopreserved prior to therapy. With these results, it will now be possible to develop novel immunotherapeutic approaches using ex vivo-expanded autologous NK cells in clinical trials in patients with high-risk ALL.

References
1. Lanier LL. NK cell recognition. Annu Rev Immunol 2005;23: 225-74.
2. Becknell B, Caligiuri MA. Interleukin-2, interleukin-15, and their roles in human natural killer cells. Adv Immunol 2005;86:209-39.
3. Soiffer RJ, Robertson MJ, Murray C, Cochran K, Ritz J. Interleukin-12 augments cytolytic activity of peripheral blood lymphocytes from patients with hematologic and solid malignancies. Blood 1993;82:2790-6.
4. Ruggeri L, Capanni M, Urbani E, et al. Effectiveness of donor natural killer cell alloreactivity in mismatched hematopoietic transplants. Science 2002;295:2097-100.