Adoptive Transfer of NK Cells Can Eradicate Residual Leukemia After BMT

The transfer of allogeneic lymphocytes given after allogeneic bone marrow transplantation (BMT) provides a beneficial antileukemic effect, the so-called graft-versus-leukemia (GVL) effect. However, T cell mediated severe graft-vs-host-disease (GVHD) remains a major problem. The aim of the present study was to determine the antileukemic potential of IL-2 activated NK cells given shortly after BMT. BALBc/mice were given a lethal dose of A20 (H-2d, B cell leukemia) cells 2 days prior to lethal total body irradiation (TBI) and transplantation of either syngeneic or allogeneic bone marrow cells. After depletion of Thy-1.2-positive T cells, either syngeneic or allogeneic IL-2 activated spleen cells were given 24 h after BMT. Injection of A20 leukemia led to death after a median of 30 days. A lethal dose of TBI followed by either syngeneic or allogeneic Thy 1.2 depleted BMT resulted in a slight antileukemic effect. The adoptive transfer of syngeneic enriched and IL-2 preincubated NK cells at the time of BMT exerted a significant GVL effect. Although the animals demonstrated no signs of GvHD, the strongest GVL effect was observed after infusion of allogeneic MHC-mismatched NK cells. The results clearly demonstrate that allogeneic NK cells offer superior antileukemic activity without mediating GVHD.