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Anti-cancer therapy for gastrointestinal canser using cytotoxic T cells and bispecific antibody

Research Project

Project/Area Number 07671359
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Digestive surgery
Research InstitutionYamagata university School of medicine

Principal Investigator

USUBA Osamu  Yamagata university School of medicine, Surgery, assistant professor, 医学部, 講師 (60185014)

Co-Investigator(Kenkyū-buntansha) KIMURA Seishi  Yamagata university School of medicine, Surgery, assistant professor, 医学部, 助手 (10234361)
Project Period (FY) 1995 – 1997
Project Status Completed (Fiscal Year 1997)
Budget Amount *help
¥2,400,000 (Direct Cost: ¥2,400,000)
Fiscal Year 1997: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 1996: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 1995: ¥700,000 (Direct Cost: ¥700,000)
KeywordsBispecific antibody / Cytotoxic T lymphocytes / Gastrointestinal canser therapy / Hybridhybridoma / HPLC / anti-CD3 antibody / Fc receptor / bispecitic / MAb(モノクローナル抗体) / 培養因子 / CTL(細胞障害性T細胞) / bispecific / MAb(モノクローナール抗体) / 接着因子 / bispcific / MAb / 細胞障害性T細胞
Research Abstract

Cytotoxic T lymphocytes can lyse Fc receptor-bearing target cells in vitro in the presence of anti-CD3 antibodies. This "redirected" lysis is not restricted by major histocompatibility antigen nor does it require nominal antigen recognition by the CTL.The efficacy of redirected lysis in vivo was assessed by comparing the survival of mice inoculated with a melanoma cell line transfected with the gene for mouse Fc receptor versus the untransfected melanoma when inoculated with syngenic mouse CTL and anti-CD3 antibody. Survival was significantly higher in the animals given injections of Fc receptor positive melanoma, CTL,and anti-CD3 monoclonal antibody. Redirected lysis does not preclude the establishment of tumor immunity, since animals that rejected the tumor as a result of redirected lysis exhibited an increased resistance to reinoculation with tumor cells.
Studies over the last several years have demonstrated that antibodies to the TCR or CD3 can activate cells in the absence of Ag an … More d MHC gene products. An alter native approach to harnessing the cytotoxic potential of CTL can be to use bispecific antibodies to direct and activate CTL of various specificities to lyse cells expressing virus or tumor Ag. Bispecific antibodies with specificity for the TCR/CD3 complex as well as to a target cell-surface Ag can redirect CTL to lyse the target cell. We have produced a hybridhybridoma, HHA6, which secretes bispecific antibodies capable of redirecting CTL to lyse influenza virus-infected target cells. When added along with CTL to virus-infected cells, these antibodies very efficientlyenhace cytotoxic abilities of CTL.Because hybridhybridomas reassort H and L chains randomly we attempted to purify bispecific antibody by using HPLC.The purification increased the potency of HHA6. This increase and removal of inhibiting antibody species. From these experimental results, we have attempted to produce human hybridhybridoma which secretes bispecific antibodies capable of redircting human CTL to lyse human tumor cells.
Because of unstableness of human hybridhybridoma, we have not succeeded in producing human bispecific antibodies redirected human CTL to destroy human target cells. Less

Report

(4 results)
  • 1997 Annual Research Report   Final Research Report Summary
  • 1996 Annual Research Report
  • 1995 Annual Research Report

Research Products

(25 results)

All Other

All Publications

  • [Publications] Kameyama J.Usuba O et al: "A new reconstruction after proximal gastrectomy and its operative recults" International gastric cancer congress proceedings. 1. 1117-1121 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] 薄場 修ら: "細胞障害性T細胞の抗腫瘍効果増強を目的としたbispecific MAbの開発" Biotherapy. 7(5). 878-880 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Moran T.M.Usuba O.etal: "Inhibition of multicycle influenza virus replication by hybrid antibody directed CTL lysis" J.Immunol. 146. 321-326 (1991)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Usuba O.Ito M.et al: "Antibody mediated redirected oytolysis against murine Melanoma cells in vivo." Canser Res.50. 6034-6038 (1990)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Moran T.M.Kuzu H.et al: "Staphylococcal Enterotoxin B-activated T cell can be redirected to inhibit multicycle virus replication" J.Immunol. 155. 759-765 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Kameyama J., Ishida H., Toyono M., Usuba O., Tsukamoto M.and Chiba M.: "A new reconstruction after proximal gast rectomy and its operative results." International gastric cancer congress proceedings. 1117-1121 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Usuba O., Kimura S., Kuzu H., Kuzu Y., Kameyama J., Bona C.A.Moran T.M.and Tsukamoto M: "Establishment of bispecific monoclonal antibody inorder to enhance anti-cnaser effect of cytotoxic T lymphocytes." Biotherapy. 7 (5). 878-880 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Mora, T.M., Usuba, O., Kuzu, H., Kuzu, Y., Schulman, J., and Bona, C.A.: "Inhibition of multicycle influenza virus replication by hybrid antibody-directed cytotoxic T lymphocyte lysis." J.Immunol.146. 321-326 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Usuba, O., Ito, M., Bona, C.A., and Moran T.M.: "Antibody-mediated redirected cytolysis against murine melanoma cell in vio" Cancer Res.50. 6034-6038 (1990)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Moran T., Toy E., Kuzu Y., Kuzu H., Isobe H.and Schulman J.: "Staphylococcal Enterotoxin B-Activated T Cell Can Be Redirected To Inhibit Multicycle Virus replication." J.Immunol. 155. 759-765 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] 薄場修, 木村青史 ら: "細胞障害性T細胞の抗癌瘍効果増強を目的としたbispecitic MAbの開" Biotherapy. 7(5). 878-880 (1993)

    • Related Report
      1997 Annual Research Report
  • [Publications] 薄場修, 塚本長 ら: "Nグライコリルノイラミン酸を有する癌開連糖脂質抗原に対するヒト型単クローン抗体とその反応特異性" Biotherapy. 6(5). 789-791 (1992)

    • Related Report
      1997 Annual Research Report
  • [Publications] Moran,T., Usuba.O.et al: "Inhibition of multicucle intluenza replication by hybrid antibody directed CTL lysis" Journal of Immunology. 146. 321-326 (1991)

    • Related Report
      1997 Annual Research Report
  • [Publications] Usuba O., Ito.M., et al: "Antibody mediated redirected cytolyisis aganst murure melanoma cells in vitro" Cancer Reseasch. 50. 6034-6038 (1990)

    • Related Report
      1997 Annual Research Report
  • [Publications] Moran T., Usuba O., et al: "A novel tezunique for production of hybridantibodie" Jousnal of Immuurlozical Methods. 129. 199-205 (1990)

    • Related Report
      1997 Annual Research Report
  • [Publications] 薄場修、木村清史ら: "細胞障害性T細胞の抗腫瘍効果増強を目的としたbispecificMAbの開発" Biotherapy. 7(5). 878-880 (1993)

    • Related Report
      1996 Annual Research Report
  • [Publications] 薄場修、塚本長ら: "Nグライコリルノイラミン酸を有する癌関連糖脂質抗原に対するヒト型単クローン抗体とその反応特異性" Biotherapy. 6(5). 789-791 (1992)

    • Related Report
      1996 Annual Research Report
  • [Publications] Moran,Usube et al: "Inhibition of multicycle influen zavirus replication by hybrid antibody dirocted CTL lucis" J.Immunol.146. 321-326 (1991)

    • Related Report
      1996 Annual Research Report
  • [Publications] Moran Usuba at el: "A Novel teghnique for production of hybrid antibodies" J.Immunol.Metliods. 129. 199-205 (1990)

    • Related Report
      1996 Annual Research Report
  • [Publications] Usuba,Ito et al: "Antibody mediated redirected cytolysis against murise melanoma cells in vobo." Cancer Research. 50. 6034-6038 (1990)

    • Related Report
      1996 Annual Research Report
  • [Publications] 薄場修.木村青史ら: "細胞障害性T細胞の抗腫瘍効果増強を目的としたDispecitic" MAbの開発。Biotherapy. 7(5). 878-880 (1993)

    • Related Report
      1995 Annual Research Report
  • [Publications] 薄場修.塚本長ら: "N・グライコリルノイラミン酸を有する癌関連糖脂質抗原に対するヒト型" 単クローン抗体とその反応特異性。Biotherapy. 6(5). 789-791 (1992)

    • Related Report
      1995 Annual Research Report
  • [Publications] Moran,Usuba,et al: "Inhibition of multicycle intluenza virus rephication by hybrid antibody directed CTL lysiz." J.lmmunol.146. 321-326 (1991)

    • Related Report
      1995 Annual Research Report
  • [Publications] Moran,Usuba,et al: "Anorel technizue for pnoduetion of hybrid antibiodies" J.Immunol.Methods. 129. 199-205 (1990)

    • Related Report
      1995 Annual Research Report
  • [Publications] Usuba,Ito et al: "Antibody mediated redirected cytolysis against murine Melanoma dlls in vivo." Cancer Res.50. 6034-6038 (1990)

    • Related Report
      1995 Annual Research Report

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Published: 1995-03-31   Modified: 2016-04-21  

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