Submitted May 22, 2006
Accepted December 11, 2006
Reduction of GVHD and enhanced anti-tumor effects after
adoptive infusion of alloreactive Ly49-mismatched NK-cells from MHC-matched donors
Andreas Lundqvist*, J. Philip McCoy, Leigh Samsel, and Richard Childs
Hematology Branch, National Heart Lung and Blood Institute, National Institutes of Health, Bethesda, MD, United States
Flow Cytometry Core Facility, National Heart Lung and Blood Institute, National Institutes of Health, Bethesda, MD, United States
* Corresponding author; email: lundqvia{at}nhlbi.nih.gov.
We investigated if an infusion of alloreactive natural killer (NK)-cells would reduce GVHD and mediate anti-tumor 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 GVHD (39% vs 100%; p<0.01), and prolonged survival (median 84 vs 39 days; p<0.01) compared to SCT recipients not receiving NK-cells. Recipients of Ly49 ligand-matched NK-cells had the same incidence of GVHD and similar survival compared to controls not receiving NK-cells. Pulmonary tumor burden was significantly (p<0.01) lower in recipients that received Ly49-mismatched or Ly49-matched NK-cells compared to recipients not receiving NK-cells. These data provide in-vivo evidence that a single infusion of alloreactive donor NK-cells reduces GVHD and mediates anti-tumor effects following MHC-matched allogeneic transplantation.
