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Development of human monoclonal antibodies using TC(Trans Chromosomic) mice

Research Project

Project/Area Number 12470347
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Obstetrics and gynecology
Research InstitutionKeio University

Principal Investigator

NOZAWA Shiro  Keio University, School of Medicine, Professor, 医学部, 教授 (90051557)

Co-Investigator(Kenkyū-buntansha) ISHIDA Isao  Kirin Brewery Co. Ltd., Planning Dept. Pharmaceutical Division, Leader, Human Antibody Section, 医薬カンパニー, プロジェクトリーダー(研究職)
KUBUSHIRO Kaneyuki  Keio University, School of Medicine, Assistant Professor, 医学部, 講師 (50170022)
TSUKAZAKI Katsumi  Keio University, School of Medicine, Associated Professor, 医学部, 助教授 (40118972)
Project Period (FY) 2000 – 2001
Project Status Completed (Fiscal Year 2001)
Budget Amount *help
¥14,000,000 (Direct Cost: ¥14,000,000)
Fiscal Year 2001: ¥6,000,000 (Direct Cost: ¥6,000,000)
Fiscal Year 2000: ¥8,000,000 (Direct Cost: ¥8,000,000)
KeywordsTC mice / humanized monoclonal antibodies / immunohistochemical staining / endometrial carcinoma / ovarian clear cell carcinoma / western blotting / ミサイル療法
Research Abstract

The current study was initiated with the strategy to develop humanized monoclonal antibodies towards cancers of the female genital system. The newly established TC (Trans Chromo) mice which express human antibodies (heavy chain and light chain K) were used to develop these antibodies. Basic investigations have been launched with implications towards future clinical applications; the following results have been obtained.
A human monoclonal antibody has been developed using as antigen an endometrial carcinoma cell line culture (SNG-S), originally established by the current research group leaders. Cell fusion was performed with PEG 4000 according to standard mouse monoclonal antibody protocols; mouse splenocytes and myeloma cells were fused at a ratio of 1:5, Hybridoma screening was carried out by immunohistochemical staining (ABC method) of endometrial carcinoma tissue sections. Staining results with the human monoclonal antibody 1-1C showed that the antibody stained approximately 70% of … More endometrial carcinoma tissue specimens while it showed almost no staining towards normal endometrial tissue specimens. In addition to positive staining of endometrial carcinoma, the antibody also showed strong reactivity with normal uterine cervical glands as well as cervical adenocarcinoma in addition to positive staining of several other cancers not related to the female genital system. Preliminary investigations to elucidate the antigenic epitope recognized by this antibody revealed that trypsin treatment of the specimens did not diminish the antibody staining while periodic acid treatment completely abolished positive staining of tissue specimens; thus a carbohydrate moiety was implicated as the possible epitope of this antibody. Furthermore, SDS-PAGE electrophoresis and western blotting of the cell lysates of the SNG-S cells revealed a positive band with the membrane fraction, denoting that the antigen recognized by 1-1C is possibly a cell surface membrane glycoprotein.
In addition to the above studies, investigations have been instigated to develop a human monoclonal antibody using as antigen an ovarian clear cell carcinoma cell line culture (RMG-1). Initial studies have revealed establishment of a monoclonal antibody which shows strong reactivity with ovarian clear cell carcinoma. Less

Report

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

    (26 results)

All Other

All Publications (26 results)

  • [Publications] Yoshibumi KANETA., et al.: "Selective cytotoxicity of adriamycin immunoconjugate of monoclonal antibody MSN-1 to endometrial adenocarcinoma in vitro and in vivo"Oncol.Rep.. 7. 1099-1106 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Shiro NOZAWA., et al.: "Gonadotropinreleasing hormone analoge therapy for peritoneal inclusion cysts after gynecological surgery"J.Obstet.Gynaecol.Res.. 26(6). 389-393 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Eiko SAITOH., et al.: "The expression of β 1, 4-garactosyltransferase in human trophoblasts"Acta Histochem.Cytochem.. 34(1). 62(A24) (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Nobuyuki SUSUMU., et al.: "Detection of chromosomal alterations in ovarian cancers using doubletargeted FISH"Acta Hictochem.Cytochem.. 34(1). 77(A39) (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Kyoko TAKEHARA., et al.: "Expressison of an isoform of the testis-specific estrogen sulfortransferase in the rine placenta during the late gestational period"Arch.Biochem.Biophys.. 394(2). 201-208 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Yuuki KOMURO., et al.: "Paclitaxel and SN-38 overcome cisplatin resistance of ovarian cancer cell lines by down-regulating the infflux system of cisplatin"Jpn.J.Cancer Res.. 92. 1241-1250 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] 青木 大輔 et al.2: "新女性医学大系41婦人科腫瘍の分子・細胞生物学"中山書店(平田 直). 452 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Yoshibumi KANETA et al 5: "Selective cytotoxicity of adriamycin immunoconjugate of monoclonal antibody MSN-1 to endometrial adenocarcinoma in vitro and in vivo"Oncol. Rep.. 7. 1099-1106 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Shiro NOZAWA et al 6: "Gonadotropin-Releasing Hormone Analoge Therapy for Peritoneal Inclusion Cysts after Gynecological Surgery"J. Obstet. Gynaecol. Res.. 26 (6). 389-393 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Eiko SAITOH et al 5: "The expression of β 1,4-garactosyltransferase in human trophoblasts"Acta Histochem. Cytochem.. 34 (1). 62 (A24) (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Nobuyuki SUSUMU et al 7: "Detection of chromosomal alterations cancers using doubletargeted FISH"Acta Histochem. Cytochem.. 34 (1). 77 (A39) (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Kyoko TAKEHARA et al 5: "Expression of an isoform of the testis-specific estrogen sulfotransferase in the rine placenta during the late gestational period"Arch. Biochem. Biophys.. 394 (2). 201-208 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Yuuki, KOMURO et al 5: "Paclitaxel and SN-38 Overcome cisplatin resistance of ovarian cancer cell lines by down-regulating the infflux system of cisplatin"Jpn. J. Cancer Res.. 92. 1241-1250 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Kyoko TAKEHARA et al. 5: "Expressison of an isoform of the testis-specific estrogen sulfortransferase in the rine placenta during the late gestational period"Arch. Biochem. Biophys.. 394・2. 201-208 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Yuuki KOMURO et al. 5: "Paclitaxel and SN-38 overcome cisplatin resistance of ovarian cancer cell lines by down-regulating the infflux system of cisplatin"Jpn. J. Cancer Res.. 92. 1241-1250 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] 小宮山 慎一 et al. 4: "わが教室における婦人科癌の化学療法"産婦人科治療. 83・3. 350-354 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] 鈴木 直 et al. 3: "腫瘍マーカーの読み方の実際-卵巣癌・子宮癌"臨床と研究. 78・11. 1978-1991 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] 久布白 兼行 et al. 4: "子宮頸部円錐切除術における妊孕脳温存"産科と婦人科. 68・8. 1024-1030 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] 青木 大輔 et al. 2: "タキサン製剤と子宮体癌"Oncol.Chemother.. 17・3. 221-225 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] 青木 大輔 et al. 2: "親女性医学大系41 婦人科腫瘍の分子・細胞生物学"中山書店(平田 直). 452 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Kaneyuki Kubushiro, et al 6: "Biological characteristics of human uterine endometrial cancer variant cells selected for blood group H type 1 antigen : adhesion to vascular endothelial cells."Acta Histocemica et Cytochemica. 33・3. 209-213 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Shinji Ohie, et al 6: "Cisplatin sensitivity of ovarian cancer in the histoculture drug response assay correlates to clinical response to combination chemotherapy with cisplatin, doxorubicin and cyclophosphamide."Anticancer Research. 20. 2049-2054 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Yoshibumi Kaneta, et al 5: "Selective cytotoxicity of adriamycin immunoconjugate of monoclonal antibody MSN-1 to endometrial adenocarcinoma in vitro and in vivo."Oncology Reports. 7. 1099-1106 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Shiro Nozawa, et al 2: "Gonadotropin-Releasing hormone analogue therapy for peritoneal inclusion cysts after gynecological surgery."The Journal of Obstetrics and Gynaecology Research. 26・6. 389-393 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] 久布白兼行 他2名: "新女性医学大系43 子宮体部の複合糖鎖"中山書店(平田直). 350 (2001)

    • Related Report
      2000 Annual Research Report
  • [Publications] 宇田川康博 他2名: "新女性医学大系43 子宮体部の複合糖鎖"中山書店(平田直). 350 (2000)

    • Related Report
      2000 Annual Research Report

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Published: 2000-04-01   Modified: 2016-04-21  

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