A metalloproteinase inhibitor prevents acute graft-versus-host disease while preserving the graft-versus-leukaemia effect of allogeneic bone marrow transplantation

We examined the effect of a hydroxamic acid-based matrix metalloproteinase inhibitor (KB-R7785), which we previously demonstrated to have a potent ame liorating effect on acute graft-versus-host disease (GVHD), and on the graf t-versus-leukaemia (GVL) effect of allogeneic bone marrow transplantation ( BMT). KB-R7785 was administered to (C57BL/6 x BALB/c) F1 (CBF1) mice that h ad been inoculated with IgE-producing B53 hybridoma cells of BALB/c origin as a model tumour, along with or without transplantation of C57BL/6 (B6) ba ne marrow cells and spleen cells (BMS), Administration of KB-R7785 without EMS significantly prolonged the survival of B53-inoculated CBF1 mice by inh ibiting the infiltration of B53 cells into the liver and spleen. Transplant ation of B6 BMS without KB-R7785 resulted in the death of most recipients d ue to acute GVHD while efficiently eliminating B53 cells, Administration of KB-R7785 along with B6 EMS resulted in a 50% survival of B53-inoculated CB F1 mice over 50 d without histological manifestations of acute GVHD or resi dual B53 cells. These results indicate the beneficial effects of KB-R7785 t hat inhibit tumour infiltration and prevent acute GVHD while preserving the GVL effect of allogeneic BMT.