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New transcatheter arterial embolization therapy for unresectable hepatocellular carcinoma using ferromagnetic iron-dextran reagents combined with anticancer drug and bispecific antibody

Research Project

Project/Area Number 11470254
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Digestive surgery
Research InstitutionTohoku University

Principal Investigator

SUZUKI Masanori  Tohoku University Hospital, Research Associate, 医学部附属病院, 助手 (70206530)

Co-Investigator(Kenkyū-buntansha) KATAYOSE Yu  Tohoku University Hospital, Research Associate, 医学部附属病院, 助手 (20302151)
ENDO Kojin  Tohoku University Hospital, Research Associate, 医学部附属病院, 助手 (70292315)
UNNO Michiaki  Tohoku University Graduate School of Medicine, Research Associate, 大学院医学系研究科, 助手 (70282043)
OSADA Yukihiro  The Institute of Physical and Chemical Research (RIKEN), Chief Investigator, 抗生物質研究室, 主任研究員(研究職) (80160836)
MIURA Shigeto  High Field Laboratory for Superconducting Materials, Institute for Materials Research, Tohoku University, Associate Professor, 強磁場超刺激伝導材料研究センター, 助教授 (90005893)
Project Period (FY) 1999 – 2000
Project Status Completed (Fiscal Year 2001)
Budget Amount *help
¥14,200,000 (Direct Cost: ¥14,200,000)
Fiscal Year 2000: ¥2,800,000 (Direct Cost: ¥2,800,000)
Fiscal Year 1999: ¥11,400,000 (Direct Cost: ¥11,400,000)
KeywordsHepatocellular carcinoma / ferromagnetic iron-dextran / Bispecific antibody / 磁性体
Research Abstract

With the aim to see the fate of unresectable tumor of the liver, we are planning to embolize the tumor feeding artery via transcatheteric route by novel embolus, ferromagnetic iron-dextran along with Reveromycine (RM) - A, which is a mitogenic inhibitor and bispecific antibody targeting for both hepatoma cells and LAK cells. This complex forms a colloid which will held at tumor site by creating a magnetic field around the tumor site. For the component of novel transcatheteric hepatic arterial embolus, we synthesized two kinds of bispecific antibodies (BsAbs), i.e., (OKXL) BsAbs constructed with both OKT-3 (anti-CD3) and L-7-6 (anti-HCC), and (3GXL) BsAbs constructed with 3-G-8 (anti-CD-16) and L-7-6 antibodies by chemical reconstruction method. The cytotoxicity was tested by MTT assay in several conditions. These two BsAbs, having pairs of binding arms on their single molecule, showed similar binding to target cells as the parental monoclonal antibodies (OKT-3, 3-G-8, L-7-6), when examined with FACS. Newly devised in vitrocytotoxicity tests revealed that LAK or PWM-simulated LAK (PWM-LAK) cells did not show any significant cytotoxic activity to HCC cells, while both effector/target (0.3) in the presence of BsAbs (OKXL) for the efficient retargeting of the effector cells. Inasmuch as PWM-LAK cells proliferate in vitro 3-5 times faster than LAK cells, adoptive immunotherapy using PWM-LAK cells in combination with (OKXL) BsAbs should be very promising.

Report

(3 results)
  • 2001 Final Research Report Summary
  • 2000 Annual Research Report
  • 1999 Annual Research Report
  • Research Products

    (15 results)

All Other

All Publications (15 results)

  • [Publications] 工藤俊雄, 鈴木正徳: "Specific targeting immunotherapy of cancer with bispecific antibodies"Tohoku J Exp Med. 188. 275-288 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] 浅野竜太郎, 鈴木正徳: "Functional construction of the anti-mucin core protein (MUC1) antibody MUSE 11 variable regions in a bacterial expression system"J. Biochem. 127. 673-679 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] 竹村真一, 鈴木正徳: "Functional Fv fragment of an antibody specific for CD28: Fv-mediated co-stimulation of T cells"FEBS Letters. 476. 266-271 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] 竹村真一, 鈴木正徳: "Construction of a diabody (small recombinant bispecific antibody) using a refolding system"Protein Engineering. 13. 583-588 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] 工藤俊雄, 鈴木正徳: "Second generation bispecific antibodies : An application to cancer immunotherapy. An application to cancer immunotherapy"Recent Research Developments in Cancer. 1. 395-402 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Kudo T, Suzuki M, Katayose Y, Masao S, Sakurai N, Kodama H, Ichiyama M, Takemura S, Yosida H, Saeki H, Saijyo S, Takahashi J, Tominaga T, Matsuno S: "Specific targeting immunotherapy of cancer with bispecific antibodies"Tonoku J Exp Med. 188. 275-288 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Asano R, Takemura S, Tsumoto K, Sakurai N, Teramae A, Ebara S, Katayose Y, Shinoda M, Suzuki M, Imai K, Matsuno S, Kudo T, Kumagai I: "Functional construction of the anti-mucin core protein (MUCI) antibody MUSE 11variable regions in a bacterial expression system"J. Biochem.. 127. 673-679 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Shinichi Takemura, Ryutaro Asano, Kouhei Tsumoto, Takashi Arai, Naoki Sakurai, Hideaki Kodama, Hiroshi Yoshida, Yu Katayose, Masanori Suzuki, Seiki Matsuno, Toshio Kudo, Izumi Kumagai: "Functional Fv fragment of an antibody specific for CD28 : Fv-mediated co-stimulatiion of T cells"FEBS letters. 476. 266-271 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Shinichi Takemura, Ryutaro Asano, Kouhei Tsumoto, Shinji Ebara, Naoki Sakurai, Yu Katayose, Hideaki Kodama, Hiroshi Yoshida, Masanori Suzuki, Kohzoh Imai, Seiki Matsuno, Toshio Kudo, Izumi Kumagai: "Construction of a diabody (small recombinant bispecific antibody) using a refolding system"Protein Engineering. 13. 583-588 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Kudo T, Suzuki M, Takemura S, Asano R, Tumoto K, Katayose Y, Shinoda M, Sakurai N, Kodama H, Ichiyama M, Yoshida H, Hayashi H, Saito S, Takahashi J, Kumagai I: "Second generation bispecific antibodies : An application to cancer immunotherapy"Recent Research Developments in Cancer. 1. 395-402 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] 鈴木正徳: "Construction of a diabody (small recombinant bispecific antibody) using a refolding system"Protein Engineering. 13・8. 583-588 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] 鈴木正徳: "Funtional Fv fragment of an antibody specific for CD28 : Fv-mediated co-stimulation of cells"FEBS Letters. 476. 266-271 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] 鈴木正徳: "SEA-scFv融合蛋白による胆管癌養子免疫療法の実験的検討"Biotherapy. 14・5. 429-431 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] 鈴木正徳: "Functional construction of the anti-mucin core protein antibody MUSE11 variable regions in a bacterial expression sytem"J.Biochem.. 127. 673-679 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] 鈴木正徳: "胆管癌に対するアデノウイルスp27kip1を用いた遺伝子治療の基礎的研究"胆道. 13・5. 395-402 (1999)

    • Related Report
      2000 Annual Research Report

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Published: 1999-04-01   Modified: 2016-04-21  

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