2001 Fiscal Year Final Research Report Summary
A metalloproteinase inhibitor prevents acute graft-versus-host disease while preserving graft-versus-leukemia effect of allogeneic bone marrow transplantation
| Project/Area Number |
11670457
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
内科学一般
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| Research Institution | JUNTENDO UNIVERSITY |
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Principal Investigator |
MIYAJIMA Hiroaki Juntendo University, School of Medicine, Research associate, 医学部, 助手 (80209907)
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| Co-Investigator(Kenkyū-buntansha) |
OKUMURA Ko Juntendo University, School of Medicine, Professor, 医学部, 教授 (50009700)
YAGITA Hideo Juntendo University, School of Medicine, Associate Professor, 医学部, 助教授 (30182306)
HIRANO Takeo Juntendo University, School of Medicine, Associate Professor, 医学部, 助教授 (10165186)
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| Project Period (FY) |
1999 – 2001
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| Keywords | GVHD / TNF-α / Fas / FasL / MPI |
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| Research Abstract |
We here examined the effect. of a hydroxamic acid-based matrix metalloproteinase inhibitor (KB-R7785), which we previously demonstrated a potent ameliorating effect on acute graft-versus-host disease (GVHD), on graft-versus-leukemia (GVL) effect of allogeneic bone marrow transplantation (BMT), KB-R7785 was administrated into (C57BL/6 x BALB/c) Fl (CBF1) mice, that had been inoculated with IgE-producing B53 hybridoma cells of BALB/c origin as a model tumor, 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 o fB6 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 50% survival of B53-inoculated CBF1 mice over 50 days without histological manifestations of acute GVHD or residual B53 cells. These results indicate beneficial effects of KB-R7785 that inhibit tumor infiltration and prevent acute GVHD while preserving the GVL effect of allogeneic BMT.
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