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Anti-human LFA-1 monoclonal antibodies for prevention of graft failure in HLA-mismatched bone marrow transplantation.

Research Project

Project/Area Number 63480233
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) YAMAGUTI Yosiko  Tohoku University, Research Institute for Tuberculosis and Cancer, 抗酸菌病研究所, 医員
MINEGISHI Masayoshi  Tohoku University, Research Institute for Tuberculosis and Cancer Instructor, 抗酸菌病研究所, 助手 (20211592)
SATO Tetsuo  Tohoku University, Research Institute for Tuberculosis and Cancer Instructor, 抗酸菌病研究所, 助手 (90170761)
TSUCHIYA Sigeru  Tohoku University, Research Institute for Tuberculosis and Cancer Associate Prof, 抗酸菌病研究所, 助教授 (30124605)
寺沢 政彦  東北大学, 抗酸菌病研究所, 助手 (80192201)
土屋 滋  東北大学, 抗酸菌病 研究所, 助教授 (90142934)
Project Period (FY) 1988 – 1989
Project Status Completed (Fiscal Year 1989)
Budget Amount *help
¥6,100,000 (Direct Cost: ¥6,100,000)
Fiscal Year 1989: ¥2,000,000 (Direct Cost: ¥2,000,000)
Fiscal Year 1988: ¥4,100,000 (Direct Cost: ¥4,100,000)
Keywordsbone marrow transplantation / LFA-1 / graft rejection / HLA-mismatch / monoclonal antibody / LFA-1 / HLA不一致 / CD_<11>a / CD_<18> / モノクローナル抗体
Research Abstract

1. Use of the anti-LFA-1 antibody to prevent graft failure in HLA-haplotype mismatched bone marrow transplantation (BMT). A patient with Fanconi anemia underwent T cell- devpleted HLA-haplotype mismatched maternal BMT because of the lack of HLA-identical donor. To prevent graft failure a murine monoclonal antibody (mAb) directed against the alpha chain of human LFA-1 was used. The mAb (25.3) was kindly supplied by Immunotech (Marseille, France). The antibody preparations were checked for sterility and lack of pyrogenicity. The mAb was given in a 6-h iv infusion m dosis of 0.1 mg/kg for consecutive days from-3 to +6 without any signs of adverse reactions. Partial;hematological reconstitution was achieved but finally resulted in graft failure. The result in Fanconi anemia is in accord with experiences in other institutions. However, no adverse reactions in the use of the anti-LFA-1 mAb encourage to continue further clinical studies in patients selected.
2. Production of mAb against human LFA-1. To obtain anti-LFA-1 mAb capable of inducing immune tolerance and available for clinical use spleen cells from BALB/C mice immunized with K4 cells were fused with SP2/0 cells. Hybridoma supernatants obtained were screened for the capability of inhibiting the aggregation of K4 cells stimulated by phorbol ester.
Three hybridoma clones secreting anti-LFA-1 antibodies were obtained; one clone was determined by flowcytometry and biochemical analysis to produce the antibody directed at a chain (MAY-035) and other two the antibodies directed at 8 chain (MAY-017, and MAY-044). The isotype of the mAbs obtained was all IgGl. The three antibodies strongly inhibited lymphocyte proliferation in response to alloantigens and mitogens.

Report

(3 results)
  • 1989 Annual Research Report   Final Research Report Summary
  • 1988 Annual Research Report
  • Research Products

    (37 results)

All Other

All Publications (37 results)

  • [Publications] Ohashi Y.et al.: "New monoclonal antibodies directed against LFAー1 αーand βーchains" Tohoku J.Exp.Med(投稿中).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] Majima T.et al.: "Unusual expression of lgG Fc receptors on peripheral granurocytes from patients with leukocyte adhesion deficiency(CD11/CD18 deficiency)" J.lmmunol.(投稿中).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] Minegishi N.et al.: "Preservation of immature hematopoietic progemitor cells responding to interleukin 3 in marrow treated with 4ーhydroーperoxyclctophosphamide" Tohoku J.Exp.Med. 159. 113-122 (1989)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] Minegishi N.et al.: "Effects of in vitro treatment with 4ーhydroーperoxy cyclophos.phamide and hyperthermia on leukemic progenitor cells" Tohoku J.Exp.Med. 159. 101-111 (1989)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] Fukudome K.et al.: "Comparison of human,semian,and bovine rotaviruses for requirement of sialic acid in hemaggluhination and cell adsorption" Virology. 172. 196-205 (1989)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] DeClercq E.et al.: "Broadーspectrum dntiviral activities of neplanocin A,3ーdeazaneplanocin A,and their 5'ーnor derivatives" Antimicrob.Agents Chemother.33. 1291-1297 (1989)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] Minegishi M et al.: "Monoclonal antibody directed to human Tーcell malignancy antigen" Leukemia Res.13. 43-51 (1989)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] Ishii A.et al.: "Chronic myelocytic leukemia probably promoted by growth hormone" Tohoku J.Exp.Med. 158. 263-264 (1989)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] Fukuhara N.et al.: "Role of VP3 in human rotavirus internalization after targetcell attachment via VP7" J.Virol. 62. 2209-2218 (1988)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] Minegishi N.et al.: "Chronic granulomatous disease with neutrophil membrane cytochrome b deficiency:demonstration by immunochemical staining with monoclonal antibodies" Tohoku J.Exp.Med. 154. 143-148 (1988)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] Minegishi M.et al.: "Characterization of precursor Tーcell line(THPー6)with rearranged Tーcell receptor β chain gene" Leukemia Res.12. 227-232 (1988)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] Ohashi Y. et al.: "New monoclonal antibodies against LFA-1 alpha and beta chains." Tohoku J. Exp. Med.

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] Majima T. et al.: "Unusual expression of IgG Fc receptors on peripheral granulocytes from patients with leukocyte adhesion deficiency (CD11/CD18 deficiency)" J. Immunol.

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] Minegishi N. et al.: "Preservation of immature hematopoietic progenitor cells responding to interleukin 3 in marrow treated with 4-hydroperoxycyclophosphamide" Tohoku J. Exp. Med. 159:113-122, 1989.

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] Minegishi N. et al.: "Effects of in vitro treatment with 4-hydroperoxycyclophosphamide and hyperthermia on leukemic progenitor cells" Tohoku J. Exp. Med. 159:101-111, 1989.

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] Minegishi M. et al.: "Monoclonal antibody directed to human T-cell malignancy antigen" Leukemia Res. 13:43-51, 1989.

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] Fukudome K. et al.: "Comparison of human, semian, and bovine rotavirus for requirement of sialic acid in hemagglutination and cell adhesion" Virology. 172:196-205, 1989.

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] De clercq E et al.: "Broad-spectrum antiviral activities of neplanocin A, 3-deazaneplanocin A, and their 5'-nor derivatives" Antimicrob. Agents Chemother. 33:1291-1297, 1989.

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] Ishii A. et al.: "Chronic myelocytic leukemia probably promoted by growth hormone" Tohoku J. Exp. Med. 158:263-264, 1989.

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] Fukuhara N. et al.: "Role of VP3 in human rotavirus internalization after target cell attachment via VP7" J. Virol. 62:2209-2218, 1988.

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] Minegishi M. et al.: "Characterization of a precursor T-cell line (THP-6) with rearranged T-cell receptor beta chain gene" Leukemia Res. 12:227-232, 1988.

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] Minegishi N. et al.: "Chronic granulomatous disease with neutrophil membrane cytochrome b deficiency : demonstration by immunochemical staining with monoclonal antibody" Tohoku J. exp. Med. 154:143-148, 1988.

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] Ohashi Y.etal.: "New monoclonal antibodies directed against LFA-1 α-and β-chains" Tohoku J.Exp.Med.

    • Related Report
      1989 Annual Research Report
  • [Publications] Majima T.et al: "Unusual expression of lgG Fc receptorss on peripheral granurocytes from patients with leukocyte adhesion deficiency(CD11/CD18 deficiency)" J.lmmunol.

    • Related Report
      1989 Annual Research Report
  • [Publications] Minegishi N.etal.: "Presevation of immature hematopoietic progenitor cells responding to interleukin 3 in marrow treated with 4-hydro Peroxy cyctophos phamide" Tohoku J.Exp.Med.159. 113-122 (1989)

    • Related Report
      1989 Annual Research Report
  • [Publications] Minegishi N.etal.: "Effects of in vitro treatment with 4-hydro-peroxy clyclophos.Phamide and hyperthermia on leukemic progenitor cells" Tohoku J.Exp.Med.159. 101-111 (1989)

    • Related Report
      1989 Annual Research Report
  • [Publications] Fukudome K.etal.: "Comparison of human,semian,and bovine rotaviruses for reguirement of sialic acid in hemaggluhnation and cell adsorption" Virology. 172. 196-205 (1989)

    • Related Report
      1989 Annual Research Report
  • [Publications] Declercq E.etal.: "Broad-spectrum antiviral activities of neplanocin A,3-deazaneplanocin A,and their 5-nor derivatives" Antimicrob.Agents Chemother.33. 1291-1297 (1989)

    • Related Report
      1989 Annual Research Report
  • [Publications] Minegishi M.etal.: "Monoclonal antibody directed to human T-cell malignancy antigen" Leukemia Res.13. 43-51 (1989)

    • Related Report
      1989 Annual Research Report
  • [Publications] Ishii A.etal.: "Chronic myelocytic lenkemia probably promoted by growth hormone" Tohoku J.Exp.Med.158. 263-264 (1989)

    • Related Report
      1989 Annual Research Report
  • [Publications] Fukuhara N.etal.: "Role of VP3 in human rotavirus internalization after target cell attachment via VP7" J.Virol.62. 2209-2218 (1988)

    • Related Report
      1989 Annual Research Report
  • [Publications] Minegishi N.etal.: "Chronic granulomatous disease with neutrophil membrane cytochrome b deficiency:demonstration by immunochemical staining with monoclonal antibodies" Tohoku J.Exp.Med.154. 143-148 (1988)

    • Related Report
      1989 Annual Research Report
  • [Publications] Minegishi M.etal.: "Characterization of precursor T-cell line(THP-6)with rearranged T-cell receptor β chain gene" Leukemia Res.12. 227-232 (1988)

    • Related Report
      1989 Annual Research Report
  • [Publications] OHASHI,Yoshiuki: Tohoku J.exp.Med.

    • Related Report
      1988 Annual Research Report
  • [Publications] MINEGISHI,Masayoshe: Lenkemia Res.12. (1988)

    • Related Report
      1988 Annual Research Report
  • [Publications] MINEGISHI,Masayoshi: Lenkemia Res. 12. 227-232 (1988)

    • Related Report
      1988 Annual Research Report
  • [Publications] MINEGISHI,Naoko: Tohoku J.exp.Med. 154. 143-148 (1988)

    • Related Report
      1988 Annual Research Report

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Published: 1988-04-01   Modified: 2016-04-21  

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