Cellular & Molecular Immunology. 2004 Feb, Vol.1, No.1, pp.12-21.
Natural Killer Cells: Biology and Clinical Use in Cancer Therapy
William H. D. Hallett1 and William J. Murphy1, 2
1Department of Microbiology and Immunology, University of Nevada
School of Medicine, University of Nevada, Reno, Reno, NV, USA.
2Corresponding Author: Department of Microbiology
and Immunology MS 199, University of Nevada School of Medicine,
University of Nevada, Reno, Reno, NV 89557, USA. Tel: 775-784-7599,
Fax: 775-784-7598, E-mail: wmurphy@unr.edu.
Natural killer (NK) cells have the ability to mediate both bone marrow rejection and promote engraftment, as
well as the ability to elicit potent anti-tumor effects. However the clinical results for these processes are still
elusive. Greater understanding of NK cell biology, from activating and inhibitory receptor functions to the role
of NK cells in allogeneic transplantation, needs to be appreciated in order to draw out the clinical potential of
NK cells. Mechanisms of bone marrow cell (BMC) rejection are known to be dependant on inhibitory receptors
specific for major histocompatibility complex (MHC) molecules and on activating receptors that have many
potential ligands. The modulation of activating and inhibitory receptors may hold the key to clinical success
involving NK cells. Pre-clinical studies in mice have shown that different combinations of activating and
inhibitory receptors on NK cells can reduce graft-versus-host disease (GVHD), promote engraftment, and
provide superior graft-versus-tumor (GVT) responses. Recent clinical data have shown that the use of
KIR-ligand incompatibility produces tremendous graft-versus-leukemia effect in patients with acute myeloid
leukemia at high risk of relapse. This review will attempt to be a synthesis of current knowledge concerning NK
cells, their involvement in BMT, and their use as an immunotherapy for cancer and other hematologic
malignancies.
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