1991 Fiscal Year Final Research Report Summary
In vivo infusion of anti-CD11a/LFA-1 antibody for prevention and treatment of severe GVHD in HLA-nonidentical bone marrow transplantation : Its serum concentrations and biological effects.
| Project/Area Number |
02454267
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| Research Category |
Grant-in-Aid for General Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
Pediatrics
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| Research Institution | Tohoku University |
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Principal Investigator |
KONNO Tasuke Tohoku University, Research Institute for Tuberculosis and Cancer, Professor., 抗酸菌病研究所, 教授 (00004846)
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| Co-Investigator(Kenkyū-buntansha) |
MINEGISHI Naoko Tohoku University, Research Institute for Tuberculosis and Cancer, Medical Assoc, 抗酸菌病研究所, 医員
MINEGISHI Masayoshi Tohoku University, Research Institute for Tuberculosis and Cancer, Associate., 抗酸菌病研究所, 助手 (20211592)
SATO Tetsuo Tohoku University, Research Institute for Tuberculosis and Cancer, Associate., 抗酸菌病研究所, 助手 (90170761)
TSUCHIYA Shigeru Tohoku University, Research Institute for Tuberculosis and Cancer, Associate Pro, 抗酸菌病研究所, 助教授 (30124605)
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| Project Period (FY) |
1990 – 1991
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| Keywords | allogeneic BMT / HLA-nonidentical dorno / GVHD / anti-CD11a / LFA-1 antibody / mouse monoclonal antibody / enzyme-linked immunosrobent assay |
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| Research Abstract |
HLA-nonidentical bone marrow transplantation (BMT) remains the only possiblility for patients for whom allogeneic BMT in the only curative approach but a HLA-identical donor can not be offered. In this context, severe graft-versus-host disease (GVHD) in case of untreated marrow transplant and graft rejection in case of T-cell depleted BMT are major obstracles. To overcome these obstrucles an anti-CD11a/LFA-1 monoclonal antibody (mAb) has been used with promising results. In this study, a patient with Fanconi's anemia underwent HLA-nonidentical, T-cell depleted BMT and an anti-CD11a/LFA-1 mAb (25.3) was used to prevent graft rejection without success to reconstitute hematopoiesis. In another patient who underwent HLA-identical BMT but suffered from steroid-resistant severe acute GVHD, the CD11a/LFA-1 mAb was given to treat the illness. With 7-day successive infusions of the antibody severe gastrointestinal illness was improved, but skin eruption was not much changed. Serum concentrations of the mAb were assayed by enzyme-linked immunosorbent assay (ELASA) established in this study. With a single 6-h infusion the serum antibody level reached a peak at 8h and then declined with an estimated half-life of 40 h. Daily infusion caused a cumulative increase of serum mAb concentration reaching a maximum at the 5th day. After discontinuation the serum mAb levels droped rapidly. During the treatment leukopenia and neutropenia developed gradually but lylmpyocyte counts remained unchanged much. CD4+ T-cell population decreased resulting in abnormally low CD4/CD8 ratios. Blastogenic responses of lymphocytes to mitogens (PHA, con A, PWM) were defective during the treatment but completely restored after stopping the infusion. The results obtained suggest that infusion of anti-CD11a/LFA-1 mAb is an alternative strategy in controlling stroid-resistant GVHD.
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