• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to previous page

Establishment of a new human monoclonal antibody using mice that produce complete human antibodies and applications to cancer treatment

Research Project

Project/Area Number 14207065
Research Category

Grant-in-Aid for Scientific Research (A)

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) SUZUKI Nao  Keio University, School of Medicine, Assistant, 医学部, 助手 (90246356)
SUSUMU Nobuyuki  Keio University, School of Medicine, Assistant Professor, 医学部, 講師 (90206459)
TSUKAZAKI Katsumi  Keio University, School of Medicine, Associated Professor, 医学部, 助教授 (40118972)
ISHIDA Isao  Kirin Brewery Co. Ltd., Planning Dept. Pharmaceutical Division, Research Planning Section, Senior Manager, 医薬カンパニー企画部, 部長代理
FUKUCHI Takeshi  Keio University, School of Medicine, Assistant, 医学部, 助手 (70245554)
Project Period (FY) 2002 – 2003
Project Status Completed (Fiscal Year 2003)
Budget Amount *help
¥29,510,000 (Direct Cost: ¥22,700,000、Indirect Cost: ¥6,810,000)
Fiscal Year 2003: ¥11,960,000 (Direct Cost: ¥9,200,000、Indirect Cost: ¥2,760,000)
Fiscal Year 2002: ¥17,550,000 (Direct Cost: ¥13,500,000、Indirect Cost: ¥4,050,000)
KeywordsKM mouse / human monoclonal antibody / endometrial cancer / O-glycan / ovarian cancer / ミサイル療法 / 糖鎖抗原 / ヒト型モノクローナル抗体 / Cross-bred TC mouse
Research Abstract

Our research group established KM mice that produce complete human antibodies while retaining antibody diversity by introduction of the complete human antibody gene to mice. These mice are able to produce human antibodies with immunization by antigen. The current investigation aimed to establish human monoclonal antibodies (hMab) that would target cancer cells with high specificity using these mice and to use these hMabs in the diagnosis and treatment of cancer.
1) Establishment of a hMab to endometrial cancer
KM mice were immunized with the endometrial cancer cell line SNG-S and a clone was selected that reacts with endometrial cancer cells (clone 10-9D) by conventional screening methods and named HMMC-1. Immunohistochemical staining revealed that the reactivity of HMMC-1 was positive in 54.6% of uterine endometrial adenocarcinoma specimens, 76.9% of uterine cervical adenocarcinoma specimens, 75% of epithelial ovarian cancer specimens, and 87.5% of peritoneal cancer specimens. Furthermo … More re, this monoclonal antibody does not react with either proliferative or secretory phase normal endometrium or normal uterine cervical samples. Thus this antibody was found to specifically recognize mullerian cancers and mullerian duct related cancers with high specificity.
Carbohydrate analysis determined that the epitope structure for this antibody is a O-linked carbohydrate structure with an extended core 1 structure, a carbohydrate structure with limited expression in humans.
2) Establishment of a hMab to ovarian cancer
KM mice were immunized with the ovarian clear cell adenocarcinoma cell line RMG-1 and by the same methodology of 1), a clone was selected that reacts with ovarian clear cell adenocarcinoma cells (clone 2-10A) and named HMOCC-1. This antibody is immunohistochemically positive with 83.2% (84/101) of epithelial ovarian cancer specimens ; by histopathological subtype, it is positive with 72.2%, 73.9%, 90% and 90% of serous, endometrioid, clear cell, and mucinous adenocarcinoma respectively.
In vitro, this, antibody was found to inhibit the attachment of peritoneal mesothelial cells and RMG-1 cells. The epitope structure of this antibody was determined to be a glycoprotein with a carbohydrate structure that does not include sialic acid. Less

Report

(3 results)
  • 2003 Annual Research Report   Final Research Report Summary
  • 2002 Annual Research Report
  • Research Products

    (58 results)

All Other

All Publications (58 results)

  • [Publications] Yutaka Tamada, et al. 3: "Model for paraaortic lymph node metastasis produced by orthotopic implantation of ovarian carcinoma cells in athymic nude mice."Eur.J.Cancer. 40・1. 158-163 (2004)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Jun Nakayama, et al. 11: "Implantation-dependent expression of trophinin by maternal fallopian tube epithelia during tubal pregnancies : possible role of human chorionic gonadotrophin on ectopic pregnancy."Am.J.Pathol.. 163・6. 2211-2119 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Akira Hirasawa, et al. 7: "Unfavorable prognostic factors associated with high frequency of microsatellite instability and comparative genomic hybridization analysis in endometrial cancer."Clin.Cancer Res.. 9・15. 5675-5682 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Takuma Fujii, et al. 9: "Peptides inhibitory for the transcriptional regulatory function of human papillomavirus E2."Clin.Cancer Res.. 9・14. 5423-5428 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Kyoto Tanaka, et al. 8: "Estrogen sulfotransferase and sulfatase : roles in the regulation of estrogen activity in human uterine endometrial carcinomas."Cancer Science. 94・10. 871-875 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Eiko Saitoh, et al. 4: "Galactosyltransferase associated with tumor in patients with ovarian cancer : factors involved in elevation of serum galactosyltransferase."Int.J.Oncol.. 23・2. 303-310 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Kouji Banno, et al. 8: "Identification of germline MSH2 gene mutations in endometrial cancer not fulfilling the new clinical criteria for hereditary nonpolyposis colorectal cancer."Cancer Genet.Cytogenet.. 146・1. 58-65 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Nobuo Masumoto, et al. 10: "p16^<INK4a> overexpression and human papillomavirus infection in small cell carcinoma of the uterine cervix."Human Pathology. 34・8. 778-783 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Mitsuya Ishikawa, et al. 10: "Correlation of p16^<INK4A> overexpression with human papillomavirus infection in cervical adenocarcinomas."Int.J.Gynecol.Pathol.. 22・4. 378-385 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Ken Ishitani, et al. 5: "p54^<nrb> acts as a transcriptional coactivator for activation function 1 of the human androgen receptor."Biochem.Biophys.Res.Commun.. 306. 660-665 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Akira Hirasawa, et al. 8: "Association of 17q21-q24 gain in ovarian clear cell adenocarcinomas with poor prognosis and identification of PPMID and APPBP2 as likely amplification targets."Clin.Cancer Res.. 9. 1995-2004 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Nobuyuki Susumu, et al. 7: "Subcellular localization of galactosyltransferase associated with tumors in endometrial and ovarian cancer cells."Acta Histchem.Cytochem.. 36・3. 205-214 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Nobuo Masumoto, et al. 8: "Papanicolaou tests and molecular analyses using new fluid-based specimen collection technology in 3000 Japanese women."Br.J.Cancer. 88・12. 1883-1888 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Masatoshi Yokoyama, et al. 11: "Prognostic factors associated with the clinical outcome of cervical intraepithelial neoplasia : a cohort study in Japan."Cancer Letters. 192・2. 171-179 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Kyoko Tanaka, et al. 6: "Expression of glycolipids bearing Lewis phenotypes in tissues and culture cells of human gynecological cancers."Jpn.J.Cancer Res.. 93・10. 1129-1137 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Hiroyuki Nakagawa, et al. 5: "Frequent detection of human papilloma viruses in cervical dysplasia by PCR single-strand DNA-conformational polymorphism analysis."Anticancer Res.. 22. 1655-1660 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Nobuyuki Susumu, et al. 5: "Application of two-color FISH with liquid-based thin-layer cytological preparations for uterine cancers."Acta Histochem.Cytochem.. 35・3. 205-205 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Yutaka Tmada, et al. 5: "Significance of MUC1 mucin expression in clear cell adenocarcinoma of the ovary."Acta Histochem.Cytochem.. 35・1. 48-48 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] 野澤 志朗, 他1名: "「1億人の過程の医学」子宮がん,卵巣がん,絨毛がん,外陰がん"主婦の友社. 392(52-61) (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] 野澤 志朗, 他1名: "「検査値から読む病理と診断計画」CA125,CA602,CA130"中外医薬社. 1622(1294-130) (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Yutaka Tamada, et al. 3: "Model for paraaortic lymph node metastasis produced by orthotopic implantation of ovarian carcinoma cells in athymic nude mice."Eur.J.Cancer. 40(1). 158-163 (2004)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Jun Nakayama, et al. 11: "Implantation-dependent expression of trophinin by maternal fallopian tube epithelia during tubal pregnancies : possible role of human chorionic gonadotrophin on ectopic pregnancy."Am.J.Pathol.. 163(6). 2211-2219 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Akira Hirasawa, et al.: "Unfavorable prognostic factors associated with high frequency of micorosatellite instability and comparative genomic hybridization analysis in endometrial cancer."Clin.Cancer Res.. 9(15). 5675-5682 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Takuma Fujii, et al.: "Peptides inhibitory for the transcriptional regulatory function of human papillomavirus E2."Clin.Cancer Res.. 9(14). 5423-5428 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Kyoko Tanaka, et al.: "Estrogen sulfotransferase and sulfatase : Roles in the regulation of estrogen activity in human uterine endometrial carcinomas."Cancer Science. 94(10). 871-875 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Mitsuya Ishikawa, et al.: "Correlation of p 16^<INK4A> overexpression with human papillomavirus infection in cervical adenocarcinomas."Int.J.Gynecol.Pathol.. 22(4). 378-385 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Kouji Banno, et al.: "Identification of germline MSH2 gene mutations in endometrial cancer not fulfilling the new clinical criteria for hereditary nonpolyposis colorectal cancer."Cancer Genet.Cytogenet.. 146(1). 58-65 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Nobuo Masumoto, et al.: "P16^<INK4a> overexpression and human papillomavirus infection in small cell carcinoma of the uterine cervix."Hum/ Pathol.. 34(8). 778-783 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Eiko Saitoh, et al.: "Galactosyltransferase associated with tumor in patients with ovarian cancer factors involved in elevation of serum galactosyltransferase."Int.J.Oncol.. 23(2). 303-310 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Ken Ishitani, et al.: "p54^<nrb> acts as a transcriptional coactivator for activation function 1 of the human androgen receptor."Biochem.Biophys.Res.Commun.. 306(3). 660-665 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Akira Hirasawa, et al.: "Association of 17q21-q24 gain in ovarian clear cell adenocarcinomas with poor prognosis and identification of PPM1D and APPBP2 as likely amplification targets."Clin.Cancer Res.. 9. 1995-2004 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Nobuyuki Susumu, et al.: "Subcellular localization of galactosyltransferase associated with tumors in endometrial and ovarian cancer cells."Acta Histochem.Cytochem.. 36(3). 205-214 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Nobuo Masumoto, et al.: "Papanicolaou tests and molecular analyses using new fluid-based specimen collection technology in 3000 Japanese women."Br.J.Cancer. 88(12). 1883-1888 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Masatoshi Yokoyama, et al.: "Prognostic factors associated with the clinical outcome of cervical intraepithelial neoplasia : a cohort study in Japan."Cancer Letters. 192(2). 171-179 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Kyoko Takehara, et al.: "Expression of glycolipids bearing Lewis phenotypes in tissues and cultured cells of human gynecological cancers."Jpn.J.Cancer Res.. 93(10). 1129-1137 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Hiroyuki Nakagawa, et al.: "Frequent detection of human papilloma viruses in cervical dysplasia by PCR single-strand DNA-conformational polymorphism analysis."Anticancer Res.. 22. 1655-1660 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Nobuyuki Susumu, et al.: "Application of two-color FISH with liquid based thin layer cytological preparations for uterine cancers."Acta Histochem.Cytochem.. 35(3). (A5)205 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Yutaka Tamada, et al.: "Significance of MUC1 mucin expression in clear cell adenocarcinoma of the ovary."Acta Histochem.Cytochem.. 35(1). 48(A-10) (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Yutaka Tamada, et al.3: "Model for paraaortic lymph node metastasis produced by orthotopic implantation of ovarian carcinoma cells in athymic nude mice."Eur.J.Cancer. 40・1. 158-163 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Jun Nakayama, et al.11: "Implantation-dependent expression of trophinin by maternal fallopian tube epithelia during tubal pregnancies : possible role of human chorionic gonadotrophin on ectopic pregnancy."Am.J.Pathol.. 163・6. 2211-2219 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Akita Hirasawa, et al.7: "Unfavorable prognostic factors associated with high frequency of micorosatellite instability and comparative genomic hybridization analysis in endometrial cancer."Clin.Cancer Res.. 9・15. 5675-5682 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Takuma Fujii, et al.9: "Peptides inhibitory for the transcriptional regulatory function of human papillomavirus E2."Clin.Cancer Res.. 9・14. 5423-5428 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Kyoko Takehara, et al.8: "Estrogen sulfotransferase and sulfatase : roles in the regulation of estrogen activity in human uterine endometrial carcinomas."Cancer Science. 94・10. 871-875 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Eiko Saitoh, et al.4: "Galactosyltransferase associated with tumor in patients with ovarian cancer : factors involved in elevation of serum galactosyltransferase."Int.J.Oncol.. 23・2. 303-310 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Kouji Banno, et al.8: "Identification of germline MSH2 gene mutations in endometrial cancer not fulfilling the new clinical criteria for hereditary nonpolyposis colorectal cancer."Cancer Genet.Cytogenet.. 146・1. 58-65 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Nobuo Masumoto, et al.10: "p16^<INK4a> overexpression and human papillomavirus infection in small cell carcinoma of the uterine cervix."Pathology. 34・8. 778-783 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Mitsuya Ishikawa, et al.10: "Correlation of p16^<INK4A> overexpression with human papillomavirus infection in cervical adenocarcinomas."Int.J.Gynecol.Pathol.. 22・4. 378-385 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Ken Ishitani, et al.5: "p54^<nrb> acts as a transcriptional coactivator for activation function 1 of the human androgen receptor."Biochem.Biophys.Res.Commun.. 306. 660-665 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Akira Hirasawa, et al.8: "Association of 17q21-q24 gain in ovarian clear cell adenocarcinomas with poor prognosis and identification of PPMID and APPBP2 as likely amplification targets."Clin.Cancer Res.. 9. 1995-2004 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Nobuyuki Susumu, et al.7: "Subcellular lacalization of galactosyltransferase associated with tumors in endometrial and ovarian cancer cells."Acta Histchem.Cytochem.. 36・3. 205-214 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Nobuo Masumoto, et al.8: "Papanicolaou tests and molecular analyses using new fluid-based specimen collection technology in 3000 Japanese women."Br.J.Cancer. 88・12. 1883-1888 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Masatoshi Yokoyama, et al.11: "Prognostic factors associated with the clinical outcome of cervical intraepithelial neoplasia : a cohort study in Japan."Cancer Letters. 192・2. 171-179 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] 野澤 志朗, 他1名: "「1億人の家庭の医学」子宮がん,卵巣がん,絨毛がん,外陰がん"主婦の友社. 392(52-61) (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Yutaka TAMADA, et al. 5: "Significance of MUC1 mucin expression in clear cell adenocarcinoma of the ovary"Acta Histochem. Cytochem.. 35・1. 48 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Nobuyuki SUSUMU, et al. 5: "Application of two-color FISH with liquid-based thin-layer cytological preparations for uterine cancers"Acta Histochem. Cytochem.. 35・3. 205 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Hiroyuki NAKAGAWA, et al. 5: "Frequent detection of human papilloma viruses in cervical dysplasia by PCR single-strand DNA-conformational polymorphism Analysis"Anticancer Research. 22. 1655-1660 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Kyoko TAKEHARA, et al. 6: "Expression of glycolipids bearing Lewis phenotypes in tissues and cultured cells of human gynecological cancers"Jpn. J. Cancer Res.. 93. 1129-1137 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] 野澤志朗, 他1名: "検査値から読む病態と診断計画"青木三千雄(中外医薬社). 1622 (2002)

    • Related Report
      2002 Annual Research Report

URL: 

Published: 2002-04-01   Modified: 2016-04-21  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi