PMID- 12893752 OWN - NLM STAT- MEDLINE DCOM- 20040114 LR - 20210206 IS - 0006-4971 (Print) IS - 0006-4971 (Linking) VI - 102 IP - 12 DP - 2003 Dec 1 TI - NK-cell purging of leukemia: superior antitumor effects of NK cells H2 allogeneic to the tumor and augmentation with inhibitory receptor blockade. PG - 4067-75 AB - Natural killer (NK) cells are composed of subsets characterized by the expression of inhibitory or activating receptors, or both, specific for different major histocompatibility complex (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 that the transplantation of mice with the purged bone marrow cells (BMCs) resulted in long-term, relapse-free survival. We have extended the investigation to assess the antitumor 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 NK cells than by syngeneic NK cells in vitro even though comparable percentages of Ly49 NK cells were present. Using allogeneic NK cells to purge leukemia-contaminating BMCs before transplantation resulted in a higher proportion of mice with long-term survival than using syngeneic NK cells. Allogeneic NK cells did not suppress hematopoietic reconstitution as measured by granulocyte/monocyte-colony-forming unit (CFU-GM), complete blood count (CBC), and donor chimerism at various days after transplantation. Inhibitory receptor blockade of allogeneic NK cells also significantly increased these antitumor effects at lower NK/tumor ratios compared with those of syngeneic NK cells. These results demonstrate that H2-allogeneic NK cells mediate more potent antitumor effects than syngeneic NK cells without adverse hematologic effects and thus may be useful in cancer therapy. FAU - Koh, Crystal Y AU - Koh CY AD - Department of Microbiology and Immunology, University of Nevada School of Medicine, Applied Research Facility, Bldg 344/MS 199, Reno, NV 89557, USA. FAU - Ortaldo, John R AU - Ortaldo JR FAU - Blazar, Bruce R AU - Blazar BR FAU - Bennett, Michael AU - Bennett M FAU - Murphy, William J AU - Murphy WJ LA - eng GR - R01 CA72669/CA/NCI NIH HHS/United States PT - Comparative Study PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Research Support, U.S. Gov't, P.H.S. DEP - 20030731 PL - United States TA - Blood JT - Blood JID - 7603509 RN - 0 (H-2 Antigens) RN - 0 (Receptors, Immunologic) RN - 0 (Receptors, KIR) SB - IM MH - Animals MH - Bone Marrow Purging/*methods MH - Bone Marrow Transplantation/methods MH - Cells, Cultured MH - Cytotoxicity, Immunologic MH - *Graft vs Leukemia Effect MH - H-2 Antigens/immunology MH - Immunotherapy, Adoptive MH - Killer Cells, Natural/*immunology/transplantation MH - Leukemia/immunology/*therapy MH - Mice MH - Mice, Inbred C57BL MH - Receptors, Immunologic/antagonists & inhibitors MH - Receptors, KIR MH - Survival Rate MH - Transplantation, Homologous MH - Transplantation, Isogeneic EDAT- 2003/08/02 05:00 MHDA- 2004/01/15 05:00 CRDT- 2003/08/02 05:00 PHST- 2003/08/02 05:00 [pubmed] PHST- 2004/01/15 05:00 [medline] PHST- 2003/08/02 05:00 [entrez] AID - S0006-4971(20)44016-9 [pii] AID - 10.1182/blood-2003-04-1367 [doi] PST - ppublish SO - Blood. 2003 Dec 1;102(12):4067-75. doi: 10.1182/blood-2003-04-1367. Epub 2003 Jul 31.