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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.

Research Project

Project/Area Number 02454267
Research Category

Grant-in-Aid for General Scientific Research (B)

Allocation TypeSingle-year Grants
Research Field Pediatrics
Research InstitutionTohoku University

Principal Investigator

KONNO Tasuke  Tohoku University, Research Institute for Tuberculosis and Cancer, Professor., 抗酸菌病研究所, 教授 (00004846)

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)
Project Period (FY) 1990 – 1991
Keywordsallogeneic BMT / HLA-nonidentical dorno / GVHD / anti-CD11a / LFA-1 antibody / mouse monoclonal antibody / enzyme-linked immunosrobent assay
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.

  • Research Products

    (15 results)

All Other

All Publications (15 results)

  • [Publications] Konno T,Ohashi Y,Tsuchiya S,Fujie H,Minegishi M.: "In vivo infusion of anti-LFA-1 antibody for treatment of steroidresistant severe aute graft-vetsus-host disease;Serum antibody kinetics and biological effects." Tohoku J.Exp.Med. (1992)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Majima T,Ohashi Y,Nagatomi R,Lizuka A,Konno T.: "Defective mononaclear celll antibody dependent cellular cytotoxicity (ADCC) in pationts with leukocyte adhesion deficiency and CD_<11>/CD18 involvement in monocyte-mediated ADCC." J.Immunol.(1992)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Ohashi Y,Tsuchiya S,Kikuchi H,Konno T.: "A novel point mutation in leukocyte adhesion deficiency A Pro-178 was substituted for Leu in the highly conserved region of CD18" Tohoku J.Exp Med.(1992)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Minegishi M,Tsuchiya S,Yamaguchi Y,Sato T,Minegishi N.Konno T.: "A Japanese family pedigree of patients with sevcre combined immunodeficiency disease with X-linked inhevitance" Jpn.J.Human Genet.36. 137-142 (1991)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Tsuchiya S,Fujie H,Konno T.: "B-lineage phenotype of by mphoblastoid cell lines from patients with X-linked agammng lobnlinemia" Tohoku j.Exp.Med.163. 289-294 (1991)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Majima T,Minegishi N,Nagatomi R,Ohashi Y,Tsuchiya S,Kobayashi K,Konno T.: "Unusual expression of lg G Fc receptors on peripheral granulocytes from patients with leukocyte adhesion deficiency (CD11/CD18 deficiency)" J.Immunol. 145. 1694-1699 (1990)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Konno T, Ohashi Y, Tsuchiya S, Fujie H, Minegishi M.: "In vivo infusion of anti-LFA-1 antibody for treatment of steroid-resistant severe acute graft-versus-host disease ; serum antibody kinetics and biological effects." Tohoku J. Exp. Med.(1992)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Majima T, Ohashi Y, Nagatomi R, Iizuka A, Konno T.: "Defective mononuclear cell antibody dependent cellular cytotoxicity (ADCC) in patients with leukocyte adhesion deficiency and CD11/CD18 involvement in monocyte mediated ADCC." J. Immunol.(1992)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Ohashi, Y, Tsuchiya S, Kikuchi H, Konno T.: "A novel point mutation in leukocyte adhesion deficiency : A proline-178 was substituted for leucin in the highly conserved region of CD18." Tohoku J. Exp. Med.(1992)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Minegishi M, Tsuchiya S, Yamaguchi Y, Sato T, Minegishi N, Konno T.: "A Japanese family pedgree of patients with severe combined immunodeficiency disease with X-linked inheritance." Jpn. J. Human Genet. 36. 137-142 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Tsuchiya S, Fujie H, Konno T.: "B-lineage phenotype of lymphoblastoid cell lines from patients with X-linked agammaglobulinemia." Tohoku J. Exp. Med.163. 289-294 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Minegishi M, Tsuchiya S, Minegishi N, Nakamura M, Abo T, Inaba T, Konno T.: "Functional and molecular characteristics of acute lylmphoblatic leukemia cells with mature T-cell phenotype from a patient with ataxia teleangiectasia." Leukemia. 5. 88-89 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Suzuki H, Kitaoka S, Konno T, Sato T.: "The localization and function of the neutralizing protein, Vp4, in human rotavirus." Tohoku J. Exp. Med.163. 73-75 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Tazawa, Y, Nakagawa M, Abukawa D, Watabe M, Tada K, Ohi R, Konno T.: "Fall and rise variations of serum GGTP in preoperative infants with biliary atresia." J. Pediat. Gastroenterol. Nutr.10. 555-558 (1990)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Majima T, Minegishi N, Nagatomi R, Ohashi Y, Tsuchiya S, Kobayashi K, Konno T.: "Unusual expression of IgG Fc reseptors on peripheral granulocytes from patients with leukocyte adhesion deficiency (CD11/CD18 deficiency)." J. Immunol.145. 1694-1699 (1990)

    • Description
      「研究成果報告書概要(欧文)」より

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Published: 1993-03-16  

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