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

1999; Wiley; Volume: 105; Issue: 1 Linguagem: Inglês

10.1111/j.1365-2141.1999.01318.x

1365-2141

Koichi Hattori, Takao Hirano, Hiroaki Miyajima, Norifumi Yamakawa, Shoji Ikeda, Kiyoshi Yoshino, Masatoshi Tateno, Kazuo Oshimi, Nobuhiko Kayagaki, Hideo Yagita∥, Ko Okumura,

Multiple Myeloma Research and Treatments

We examined the effect of a hydroxamic acid‐based matrix metalloproteinase inhibitor (KB‐R7785), which we previously demonstrated to have a potent ameliorating effect on acute graft‐versus‐host disease (GVHD), and on the graft‐versus‐leukaemia (GVL) effect of allogeneic bone marrow transplantation (BMT). KB‐R7785 was administered to (C57BL/6 × BALB/c) F1 (CBF1) mice that had 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) bone marrow cells and spleen cells (BMS). Administration of KB‐R7785 without BMS significantly prolonged the survival of B53‐inoculated CBF1 mice by inhibiting the infiltration of B53 cells into the liver and spleen. Transplantation of B6 BMS without KB‐R7785 resulted in the death of most recipients due to acute GVHD while efficiently eliminating B53 cells. Administration of KB‐R7785 along with B6 BMS resulted in a 50% survival of B53‐inoculated CBF1 mice over 50 d without histological manifestations of acute GVHD or residual B53 cells. These results indicate the beneficial effects of KB‐R7785 that inhibit tumour infiltration and prevent acute GVHD while preserving the GVL effect of allogeneic BMT.