Reduction of GVHD and enhanced antitumor effects after adoptive infusion of alloreactive Ly49-mismatched NK cells from MHC-matched donors.
We investigated if an infusion of alloreactive natural killer (NK) cells would reduce GVHD and mediate antitumor effects in mice undergoing MHC-matched allogeneic stem cell transplantation (SCT). Balb/c mice bearing RENCA tumors underwent an allogeneic SCT from MHC-matched B10.d2 donors and were given a single infusion of either Ly49 ligand-matched, ligand-mismatched, or no donor NK cells. Recipients of Ly49 ligand-mismatched NK cells had a reduced incidence of graft-versus-host disease (GVHD; 39% vs 100%; P < .01), and prolonged survival (median 84 days vs 39 days; P < .01) compared with SCT recipients not receiving NK cells. Recipients of Ly49 ligand-matched NK cells had the same incidence of GVHD and similar survival compared with controls not receiving NK cells. Pulmonary tumor burden was significantly (P < .01) lower in recipients that received Ly49-mismatched or Ly49-matched NK cells compared with recipients not receiving NK cells. These data provide in vivo evidence that a single infusion of alloreactive donor NK cells reduces GVHD and mediates antitumor effects following MHC-matched allogeneic transplantation.
Lundqvist
Andreas
A
Hematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, 10 Center Drive, Bethesda, MD 20892, USA.
McCoy
J Philip
JP
Samsel
Leigh
L
Childs
Richard
R
D000818:Animals; D000950:Antigens, Ly; D006086:Graft vs Host Disease / Q000473:pathology / Q000628:therapy*; D020350:Graft vs Tumor Effect; D015395:Histocompatibility Antigens Class I; D007694:Killer Cells, Natural / Q000637:transplantation*; D037181:Lectins, C-Type; D008175:Lung Neoplasms / Q000473:pathology / Q000628:therapy*; D017710:Lymphocyte Transfusion; D051379:Mice; D008807:Mice, Inbred BALB C; D055630:Receptors, NK Cell Lectin-Like; D033581:Stem Cell Transplantation; D014184:Transplantation, Homologous; D047368:Tumor Burden
D000950:Antigens, Ly; D015395:Histocompatibility Antigens Class I; D037181:Lectins, C-Type; D055630:Receptors, NK Cell Lectin-Like