ALLOGENEIC MHC-MISMATCHED ACTIVATED NATURAL-KILLER-CELLS ADMINISTEREDAFTER BONE-MARROW TRANSPLANTATION PROVIDE A STRONG GRAFT-VERSUS-LEUKEMIA EFFECT IN MICE

Allogeneic lymphocytes administered with an unmanipulated bone marrow transplant provide a strong antileukaemic effect, the so-called graft- versus-leukaemia (GVL) effect. On the other hand, T-cell-mediated graf t-versus-host-disease (GVHD) observed after transplantation of unmanip ulated BM graft causes substantial morbidity and mortality. The aim of the present study was to determine the antileukaemic potential of enr iched IL-2 activated NK cells administered 2 h after BMT. Balb/c (H-2( d)) mice were given a dose of A20 (H-2(d), B-cell leukaemia) cells 2 d prior to lethal total body irradiation (TBI) and transplantation of e ither syngeneic or allogeneic anti-Thy1.2 (CD90) depleted bone marrow cells. Either syngeneic (Balb/c, H-2(d)) or allogeneic (C57BL/6, H-2(b )) enriched and IL-2 (200 U/ml for 24 h) activated NK cells were given 2 h after BMT. Injection of A20 leukaemia into normal Balb/c recipien ts led to death after a median of 14 d. A lethal dose of TBI followed by either syngeneic or allogeneic Thy1.2-depleted BMT resulted in a mo dest antileukaemic effect. The adoptive transfer of syngeneic enriched and IL-2 preincubated NK cells given at time of BMT exerted a signifi cantly better GVL effect. However, the infusion of allogeneic enriched NK cells resulted in a stronger GVL effect. These results clearly dem onstrate that allogeneic NK cells are superior to syngeneic NK cells i n their potential to eradicate residual leukaemia cells after BMT with out mediating clinical overt GVHD. This experimental setting may offer a strategy for treatment of haematological malignancies in a phase of minimal residual disease.