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Analysis of antigen to renal cell carcinoma and establishment of cancer specific antibody teratment

Research Project

Project/Area Number 18591777
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Urology
Research InstitutionFujita Health University

Principal Investigator

SHIROKI Ryoichi  Fujita Health University, SCHOOL OF MEDICINE, UROLOGY, ASSOCIATE PROFESSOR (70226330)

Co-Investigator(Kenkyū-buntansha) HOSHINAGA Kiyotaka  FUJITA HEALTH UNIVERSITY, SCHOOL OF MEDICINE, UROLOGY, PROFESSOR AND CHAIRMAN (30229174)
AKAHORI Yasushi  FUJITA HEALTH UNIVERSITY, INSTITUTE FOR COMPREHENSIVE MEDICAL SCIENCE, ASSISTANT PROFESSOR (80221711)
KUROSAWA Yoshikazu  FUJITA HEALTH UNIVERSITY, INSTITUTE FOR COMPREHENSIVE MEDICAL SCIENCE, PROFESSOR (10109259)
Project Period (FY) 2006 – 2007
Project Status Completed (Fiscal Year 2007)
Budget Amount *help
¥4,010,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥510,000)
Fiscal Year 2007: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Fiscal Year 2006: ¥1,800,000 (Direct Cost: ¥1,800,000)
KeywordsRenal cell Cancer / Antibody therapy / Cancer-specific antigen / Phage library
Research Abstract

Renal cell cancer (RCC) has a heterogeneous clinical presentation with up to 30% metastatic cases at initial diagnosis and 30% of initially organ-confined cases developing metastases during follow-up at variable intervals. Recently antibodies against specific molecules have been applied for clinical treatment to malignant diseases. Although several murine monoclonal antibodies (mAbs) which have been humanized became useful therapeutic agents against a few malignancies, therapeutic Abs are not yet available for the majority of the human cancers due to our lack of knowledge which antigens (Ags) can become useful targets. In the present study we established a procedure for comprehensive identification of such Ags through the extensive isolation of human mAbs that may become therapeutic. Using the phage-display Ab library we isolated a large number of human mAbs that bind to the surface of RCC cells. They were individually screened by immunostaining and clones that preferentially and strongly stained the malignant cells were chosen. The Ags recognized by those clones were isolated by immunoprecipitation and identified by mass spectrometry. We isolated 357 mAbs with unique sequences and identified 7 distinct. Ags highly expressed on several carcinomas. After preparing complete IgGi Abs the in vitro assay for antibody-dependent cell-mediated cytotoxicity (ADCC) and the in vivo assay in cancer-bearing athymic mice were performed to examine anti tumor activity. The mAbs converted to IgG1 revealed effective ADCC as well as and tumor activity in vivo. Thus, the procedure adopted in our study enabled us to succeed in comprehensive identification of tumor-associated antigens (TAAs) and simultaneous isolation of mAbs against RCC. Therefore, we believe that some Ags detected will be useful targets for cancer therapy and several mAbs will become useful therapeutic agents to RCC in the foreseeable future.

Report

(3 results)
  • 2007 Annual Research Report   Final Research Report Summary
  • 2006 Annual Research Report
  • Research Products

    (23 results)

All 2007 2006 Other

All Journal Article (17 results) (of which Peer Reviewed: 6 results) Presentation (6 results)

  • [Journal Article] Isolation of therapeutic human monoclonal antibodies for varicella-zoster virus and the effect of light chains on the neutralizing activity2007

    • Author(s)
      Suzuki K, Akahori Y, et. al.
    • Journal Title

      J Med Virol. 79

      Pages: 852-62

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Functional analysis of anti-EGFR antibodies hor human renal cell carcinoma.2007

    • Author(s)
      Sato N, Shiroki R, Kurosawa G, Hoshinaga K, Kurosawa Y, et. al.
    • Journal Title

      Bulletin of the Fujita Medical Society 31(2)

      Pages: 121-124

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Isolation of therapeutic human monoclonal antibodies for varicella-zoster virus and the effect of light chains on the neutralizing activety.2007

    • Author(s)
      Suzuki K, Akahori Y, et. al.
    • Journal Title

      J Med Virol 79

      Pages: 852-62

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Effectiveness of Taxanes-based chemotherapy against hormone-refractory prostate carcinoma.2006

    • Author(s)
      Shiroki R, Kuwahara Y, Hoshinagaet al.
    • Journal Title

      Hinyoukika Kiyo 52

      Pages: 481-485

    • NAID

      120002141645

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Genomewide expression profiles of rat model renal isografts from brain dead donors.2006

    • Author(s)
      Kusaka M, K, Shiroki R, Kurahashi H, Hoshinagaet al.
    • Journal Title

      Transplantation 83(1)

      Pages: 62-70

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] ホルモン不応性前立腺癌に対するタキサン系薬剤の有効性2006

    • Author(s)
      白木良一, 桑原勝孝, 桜井孝彦, 丸山高広, 星長清隆
    • Journal Title

      泌尿器科紀要 52

      Pages: 481-485

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Is pulsatile perfusion necessary for renal transplantation engrafting kidneys from cardiac death donous?2006

    • Author(s)
      Kusaka M, Kubota Y, Sasaki H, Maruyama T, Hayakawa K, Shiroki R, Hoshinaga K
    • Journal Title

      Transplantation Proceeding 38・10

      Pages: 3388-3389

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Up-regulation of osteopontin, chemokines, adhesion molecule, and heat shock proteins in 1-hour biopsy from cardiac death donor kidneys2006

    • Author(s)
      Kusaka M, Kuroyanagi Y, Mori T, Sasaki H, Maruyama T, Hayakawa K, Shiroki R, Kurahashi H, Hoshinaga K
    • Journal Title

      Transplantation Proceeding 38・10

      Pages: 3347-50

    • Related Report
      2006 Annual Research Report
  • [Journal Article] The effect of patient age and some other factors on the maintenance of permanent hemodialysis vascular access2006

    • Author(s)
      Hayakawa K, Kubota Y, Sasaki H, Kusaka M, Maruyama T, Shiroki R, Hoshinaga K
    • Journal Title

      Transplantation Proceeding 38・10

      Pages: 3382-3383

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Genomewide expression profiles of rat model renal isografts from brain dead donors.2006

    • Author(s)
      Kusaka M, Kuroyanagi Y, Kowa H, Nagao K, Mori T, Yamada K, Shiroki R, Kurahashi H, Hoshinaga
    • Journal Title

      Transplantation 83・1

      Pages: 62-70

    • Related Report
      2006 Annual Research Report
  • [Journal Article] 会陰式根治的前立腺全摘除術2006

    • Author(s)
      白木良一
    • Journal Title

      臨床泌尿器科 60・6

      Pages: 351-359

    • NAID

      40007254884

    • Related Report
      2006 Annual Research Report
  • [Journal Article] 維持透析中の進行性腎癌骨転移例に対するゾレドロン酸投与の経験

    • Author(s)
      有馬 聡、白木 良一、星長 清隆, 他
    • Journal Title

      日本泌尿器科学会雑誌 (印刷中)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Comprehensive screening for antigens overexpressed on carcinomas via isolation of human monoclonal antibodies that may be therapeutic

    • Author(s)
      Gene Kurosawa, Yasushi Akahoril, Ryoichi Shiroki, Kiyotaka Hoshinaga, Yoshikazu Kurosawa
    • Journal Title

      Proceedings of the National Academy of Sciences (In press)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Comprehensive screening for antigens overexpressed on carcinomas via isolation of human monoclonal antibodies that may be therapeutic.

    • Author(s)
      Gene Kurosawa, Yasushi Akahoril, Ryoichi Shiroki, Kiyotaka Hoshinaga, Yoshikazu Kurosawa, et. al.
    • Journal Title

      Proceedings of the National Academy of Sciences. (in press)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Zoledronic acid for bone metastases due to advanced renal cell carcinoma under chronic hemodialysis.

    • Author(s)
      Arima A, K, Shiroki R, Kusaka M, Hoshinagaet al.
    • Journal Title

      Japanese J Urol. (in press)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] 維持透析中の進行性腎癌骨転移例に対するゾレドロンサン投与の経験

    • Author(s)
      有馬敏、白木良一、星長清隆、他
    • Journal Title

      日本泌尿器科学会誌 (印刷中)

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Comprehensive screening for antigens overexpressed on carcinomas via isolation of human monoclonal antibodies that may be therapeutic.

    • Author(s)
      Gene Kurosawa, Yasushi Akahori, Ryoichi Shiroki, Kiyotaka Hoshinaga, Yoshikazu Kurosawa
    • Journal Title

      Proceeding of the National Academy of Sciences (In press)

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Presentation] Oral thalidomide in combination with interleukin-2 for patients with metastatic renal cell carcinoma refractory to prior IL-2 and alpha-interferon treatment.2007

    • Author(s)
      Shiroki R, Mori S, Arima S, Miyakawa S, Ichino M, Hirano M, Kusaka M, Hayakawa K, Ishikawa K, Hoshinaga K.
    • Organizer
      29Congress of the Societe Internationale d'Urologie
    • Place of Presentation
      Paris, France
    • Year and Date
      2007-09-02
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Comprehensive isolation of complete human antibodies bound to renal cell carcinoma associated antigen2007

    • Author(s)
      N Sato, R Shiroki, K Hoshinaga, et. al.
    • Organizer
      米国泌尿器科学会(AUA)
    • Place of Presentation
      アナハイム、米国
    • Year and Date
      2007-05-20
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Comprehensive isolation of complete human antibodies bound to renal cell carcinoma associated antigen.2007

    • Author(s)
      Sato N, Shiroki R, Hoshinaga K, Kurosawa Y, et. al.
    • Organizer
      American Urological Association
    • Place of Presentation
      Anaheim CA, U.S.A.
    • Year and Date
      2007-05-20
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Comprehensive isolation of complete human antibodies bound to renal cell carcinoma associated antigen.2007

    • Author(s)
      N Sato, R Shiroki, K Hoshinaga, et. al.
    • Organizer
      米国泌尿器科学会(AUA)
    • Place of Presentation
      アナハイム、米国
    • Year and Date
      2007-05-20
    • Related Report
      2007 Annual Research Report
  • [Presentation] Comprehensive isolation of complete human antibodies bound to renal cell carcinoma.2007

    • Author(s)
      Sato N, N Sato, R Shiroki, Kurosawa Y, K Hoshinaga, et. al.
    • Organizer
      95 Japanese Society of Urology
    • Place of Presentation
      Kobe, Japan
    • Year and Date
      2007-04-14
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Hand-assisted radical retroperitoneoscopic nephroureterectomy for upper urinary tract transitional cell carcinoma : technical modification to avoid local and urinary tract recurrences.2006

    • Author(s)
      Shiroki R, Maruyama T, Ohki T, Kuwahara Y, Kusaka M, Hayakawa K, Hoshinaga K.
    • Organizer
      4th World Congress of Endourology
    • Place of Presentation
      Cleveland, CL, U.S.A.
    • Year and Date
      2006-08-17
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary

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Published: 2006-04-01   Modified: 2016-04-21  

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