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Prepublished online as a Blood First Edition Paper on July 31, 2003; DOI 10.1182/blood-2003-04-1367.
Submitted May 1, 2003
Accepted June 12, 2003
NK cell purging of leukemia: superior anti-tumor effects of NK cells H2-allogeneic to the tumor and augmentation with inhibitory receptor blockade
Crystal Y Koh, John R Ortaldo, Bruce R Blazar, Michael Bennett, and William J Murphy*
Laboratory of Molecular Immunoregulation, National Cancer Institute, Frederick, MD, USA
Experimental Immunology Laboratory, National Cancer Institute, Frederick, MD, USA
Cancer Center and Department of Pediatrics, Division of Blood and Marrow Transplantation, University of Minnesota, Minneapolis, MN, USA
Department of Pathology, University of Texas Southwestern Medical Center, Dallas, TX, USA
Department of Microbiology and Immunology, University of Nevada, Reno, NV, USA
* Corresponding author; email: wmurphy{at}unr.edu.
NK cells are composed of subsets characterized by expression of inhibitory and/or activating receptors specific for different MHC class I determinants. We have previously shown that inhibitory receptor blockade of syngeneic NK cells was an effective means of ex vivo purging of leukemia contaminated bone marrow, and transplantation of mice with the purged bone marrow cells (BMC) resulted in long-term, relapse-free survival. We have extended the investigation to assess the anti-tumor effects mediated by NK cells H2-allogeneic to tumor cells. We demonstrate that various tumor cell lines are more susceptible to lysis by H2-allogeneic versus syngeneic NK cells in vitro even though comparable percentages of Ly49 NK cells were present. Use of allogeneic NK cells to purge leukemia contaminating BMC prior to transplantation resulted in higher proportion of mice with long-term survival compared to the use of syngeneic NK cells. Allogeneic NK cells did not suppress hematopoietic reconstitution as measured CFU-GM, CBC, and donor chimerism at various days after transplantation. Inhibitory receptor blockade of allogeneic NK cells also significantly increased these anti-tumor effects at lower NK:tumor ratios compared to that of syngeneic NK cells. These results demonstrate that H2-allogeneic NK cells mediate more potent anti-tumor effects than syngeneic NK cells without adverse hematologic effects and thus may be useful in cancer therapy.
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