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Immunotargeting-therapy for bile duct carcinoma using human type bispecific antibody

Research Project

Project/Area Number 04670756
Research Category

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

Allocation TypeSingle-year Grants
Research Field Digestive surgery
Research InstitutionTohoku University School of Medicine

Principal Investigator

SUZUKI Masanori  1st Dept.of Surg., Tohoku Univ.Sch.of Med., Assistant Prof., 医学部, 助手 (70206530)

Co-Investigator(Kenkyū-buntansha) 大内 清昭  東北大学, 医学部, 助教授 (20124555)
蝦名 宣男  東北大学, 医学部・附属病院, 助手 (40185137)
Project Period (FY) 1992 – 1994
Project Status Completed (Fiscal Year 1994)
Budget Amount *help
¥2,200,000 (Direct Cost: ¥2,200,000)
Fiscal Year 1994: ¥400,000 (Direct Cost: ¥400,000)
Fiscal Year 1993: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 1992: ¥900,000 (Direct Cost: ¥900,000)
KeywordsBile duct carcinoma / Bispecific antibody / Adoptive immunotherapy / 養子免疫療法 / Bispecific antibody / Bile duct carcinoma / SCID mouse / Human monoclonal antibody / Human monoclonel antibody / Bill dnct cacuinoma
Research Abstract

Our strategy to generate human monoclonal antibodies (HMAbs) consist of cell fusion between a parental B cell line (Kudo et al., 1994) and EBV-transformed B cell line from transferred lymphocytes of bile duct cancer patient or healthy volunteers into SCID mouse to allow in vivo stimulation of human lymphocytes against allogenic bile duct cancer cell line TFK-1 (Saijo et al., manuscript in preparation). At present, we obtain several HMAbs, but they weakly reacted with the surface of TFK-1. These HMAbs were not suitable for specific targeting therapy because of there weak reactivity. So we could not start to investigate the effect of a bispecific antibody (BsAb) against TFK-1. We need more time to develop strongly reactive HMAbs with TFK-1. We have investigated the effect of BsAb in vitro and in vivo using monoclonal antibody (L-7-6) against hepatocellular carcinomas (HCC) as a preliminary experiment. Two type of BsAb, L-7-6 x anti-CD3 and L-7-6 x anti-CD16, was made by chemical conjugat … More ion. LAK cells, as effector cells, were obtained as follows. In brief, Peripheral blood mononuclear cells, isolated from heparinized blood of a bile duct cancer patient or a healthy volunteer by density gradient centrifugation, were cultured for 48 h in RPMI-1640 supplemented with 10% FBS and 100U/ml recombinant human IL-2 at a cell density of 1 x 10^6/ml, in a culture flask, where bottom was precoated with OKT-3 MoAb (10mg/ml) for induction of LAK cells.
Result as follows ; In vitro experiment, percent cytotoxicity for three HCC cell lines ranged from 20-80%, even at a low E/T ratio (0.3-4) with only 0.1 mu g/ml of BsAb. On the other hand, without BsAb, percent cytotoxicity was only 5-20% at the same E/T ratio. The maximal discrepancy between using BsAb an without BsAb was reached at about 60%. This indicted that LAK cells with BsAb greatly enhanced cytotoxicity.
In this study, we clearly demonstrate that BsAbs have a potent effect of cytotoxicity in vitro. At Winn's assay in vivo, we have an impression that the growth of human HCC cell lines with LAK cells and BsAb in more slower than without BsAb on SCID mouse. Next, we are going to verify whether LAK cells with BsAb can kill the tumor cells after establishing xenografted human HCC cell line into mouse subcutaneous tissue by intravenous injection of LAK cells with BsAb. Less

Report

(4 results)
  • 1994 Annual Research Report   Final Research Report Summary
  • 1993 Annual Research Report
  • 1992 Annual Research Report
  • Research Products

    (13 results)

All Other

All Publications (13 results)

  • [Publications] 西條 進: "肝細胞癌に対するBiapecific抗体の作製と抗腫瘍効果に対する検討" 日本癌学会総会記事第53回. 53. 444- (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] 西條 進: "肝細胞癌に対するBispefic抗体の作製と抗腫瘍効果に関する検討" 日本外科学会雑誌 第94回日本外科学会総会号. 95. 321- (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] 西條 進: "肝細胞癌に対する新しい養子免疫療法の試み〜Bispecific抗体を用いたImmuno-tirgeting thuapy" 第30回日本肝臓学会総会 日本肝臓学会誌. 35. 359- (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Susumu Saijo: "Retargetivy of PWM-LAK cells wioh Bispecific Antibodies Creatly Enhances Cytotoxicity to atepato cellular carcivom" Jap.J.Cancer Research.(in press).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Susumu Saijo: "Establish ment of New Extrahepatei Bile Out Caranoma Cell Line,TFK-1" Ccll. (in press).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Masanori Suzuki: "Perineural tumor invasion and its relation with the lymphogenous spreaol in human and oxperiuental careinoma of bile duit" Tohobu J. Exp.Med. 172. 17-28 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Susumu Saijo: "Retargeting of PWM-LAK Cells with Bispecific Antibodies Research Greatly Enhances Cytotoxicity to Hepatocellular Carcinoma" Jpn.J.Cancer Research. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Susumu Saijo: "Establishment of a New Extrahepatic Bile Duct Carcinoma Cell Line, TFK-1" Cell. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Masanori Suzuki: "Perineural tumor invasion and its relation with the lymphogenous spread in human and experimental carcinoma of bile duct" Tohoku J.Exp.Med.172. 17-28 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] 西條進: "肝細胞癌に対するBispecific抗体の作製と抗腫瘍効果に対する検討" 日本癌学会総会記事 第53回. 53. 444- (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] 西條進: "肝細胞癌に対するBispecific抗体の作製と抗腫瘍効果に関する検討" 日本外科学会雑誌 第94回日本外科学会総会号. 95. 321- (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] 西條進: "肝細胞癌に対する新しい養子免疫療法の試み Bispecific抗体用いたImmuno-tarjeting therapy" 第30回日本肝臓学会総会 日本肝臓学会誌. 35. 359- (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] 鈴木正徳: "Perineural Tumor Invasion and Its Relation with the Lymphogenous Spread in Human and Experimental Carcinoma of Bile Duct.A Computer-aided3-D Reconstruction Study" Tohoku J.Exp Med.,. 172. 17-28 (1994)

    • Related Report
      1994 Annual Research Report

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Published: 1992-04-01   Modified: 2016-04-21  

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