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DEVELOPMENT OF TAILORED-MADE TYPE PROSTATE CANCER GENE THERAPY AIMING AT SYSTEMIC IMMUNE-ACTIVATION

Research Project

Project/Area Number 15209052
Research Category

Grant-in-Aid for Scientific Research (A)

Allocation TypeSingle-year Grants
Section一般
Research Field Urology
Research InstitutionOkayama University

Principal Investigator

KUMON Hiromi  Okayama University, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Professor, 大学院・医歯薬学総合研究科, 教授 (30144760)

Co-Investigator(Kenkyū-buntansha) NASU Yasutomo  Okayama University, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Associate Professor, 大学院・医歯薬学総合研究科, 助教授 (20237572)
NAKAYAMA Eiichi  Okayama University, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Professor, 大学院・医歯薬学総合研究科, 教授 (60180428)
YAMADA Masao  Okayama University, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Professor, 大学院・医歯薬学総合研究科, 教授 (40166731)
FUJIWARA Toshiyoshi  Okayama University, University Hospital of Medicine and Dentistry, Associate Professor, 医学部・歯学部附属病院, 助教授 (00304303)
EBARA Shin  Okayama University, University Hospital of Medicine and Dentistry, Research Assistant, 医学部・歯学部附属病院, 助手 (70379741)
津島 知靖  岡山大学, 大学院・医歯学総合研究科, 助教授 (20135990)
Project Period (FY) 2003 – 2005
Project Status Completed (Fiscal Year 2005)
Budget Amount *help
¥41,470,000 (Direct Cost: ¥31,900,000、Indirect Cost: ¥9,570,000)
Fiscal Year 2005: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2004: ¥16,120,000 (Direct Cost: ¥12,400,000、Indirect Cost: ¥3,720,000)
Fiscal Year 2003: ¥20,930,000 (Direct Cost: ¥16,100,000、Indirect Cost: ¥4,830,000)
Keywordsprostate cancer / gene therapy / adenovirus vector / tumor associated antigen / HV-tk / NY-ESO-1 / dendritic cell / 自殺遺伝子 / Interleukin-12
Research Abstract

This research has been conducted for the purpose of developing the tailored-made type of prostate cancer gene therapy activating tumor specific systemic immunity. We achieved following resuts
1)Clinical trial of prostate cancer gene therapy
We performed prostate cancer gene therapy using intraprostatic injection of adenoviral vector expressing HSV-tk gene and systemic administration of Ganciclovir and analyzed immunological profile of each patient in addition to clinical safety and efficacy. Clinical safety and efficacy were confirmed in 9 cases. Serum cytokine level did not change significantly before and after gene therapy. Interestingly peripheral blood CD8+/HLA-DR+ increased after treatment indicating systemic activation of cell mediated immunity.
2)Expression analysis of tumor associated antigen in prostate cancer
Expression of NY-ESO-1,SSX in prostate cancer were analyzed and its host immune reaction based of tissue expression were also checked. As a result it was suggested that NY-ESO-1,SSX can be a target for the prostate cancer immunotherapy.
3)Clinical trial of immunotherapy
Peptid pulsed dendritic cell therapy and NY-ESO-1 protein immuno-therapy were conducted. Clinical safety and clinical activity were confirmed. Tumor specific immune response were also observed in some cases.
4)Interleukin-12 immuno gene therapy(extensive research)
Usefulness of adjuvant and neo-adjuvant application of IL- 12 gene therapy was confirmed as a extensive collaboration Baylor College of Medicine.

Report

(4 results)
  • 2005 Annual Research Report   Final Research Report Summary
  • 2004 Annual Research Report
  • 2003 Annual Research Report
  • Research Products

    (22 results)

All 2006 2005 2004 2003 Other

All Journal Article (19 results) Publications (3 results)

  • [Journal Article] Therapeutic effects of adoptive splenocyte transfer following in situ AdlL-12 gene therapy in a mouse prostate cancer model2006

    • Author(s)
      Saika T., Kumon H.
    • Journal Title

      Cancer Gene Therapy 13(1)

      Pages: 91-98

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Therapeutic effects of adoptive splenocyte transfer following in situ AdIL-12 gene therapy in a mouse prostate cancer model.2006

    • Author(s)
      Saika T., Kusaka N., Mouraviev V., Satoh T., Kumon H., Timme TL., Thompson TC.
    • Journal Title

      Cancer Gene Therapy 13(1)

      Pages: 91-98

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Therapeutic effects of adoptive splenocyte transfer following in situ AdIL-12 gene therapy in a mouse prostate cancer model2006

    • Author(s)
      T.Saika, H.Kumon et al.
    • Journal Title

      Cancer Gene Therapy 13

      Pages: 91-98

    • Related Report
      2005 Annual Research Report
  • [Journal Article] XAGE-1 mRNA expression in prostate cancer and antibody response in patients.2005

    • Author(s)
      Koizumi F., Kumon H.
    • Journal Title

      Microbiol Immunol. 49(5)

      Pages: 471-476

    • NAID

      10015708346

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Adenovirus-mediated overexpression of REIC/Dkk-3 selectively induces apoptosis in human prostate cancer cells through activation of c-Jun-NH2-Kinase.2005

    • Author(s)
      Abarzua F., Nasu Y., Kumon H.
    • Journal Title

      Cancer Research 65(21)

      Pages: 9617-9622

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Adeno-Associated Virus 2-Mediated intratumoral prostate cancer gene therapy : Long-term maspin expression efficiently suppresses tumor growth.2005

    • Author(s)
      Watanabe M., Nasu Y., Kumon H
    • Journal Title

      Human Gene Therapy 16

      Pages: 699-710

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] XAGE-1 mRNA expression in prostate cancer and antibody response in patients.2005

    • Author(s)
      Koicumi F., Noguchi Y., Saika T., Nakagawa K., Sato S., Eldib A.M.A., Nasu Y., Kumon H., Nakayama E.
    • Journal Title

      Microbiol Immunol. 49(5)

      Pages: 471-476

    • NAID

      10015708346

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Adenovirus-mediated overexpression of REIC/Dkk-3 selectively induces apoptosis in human prostate cancer cells through activation of c-Jun-NH2-Kinase.2005

    • Author(s)
      Abarzua F., Sakaguchi M., Takaishi M., Nasu Y., Kurose K., Ebara S., Miyazaki M., Namba M., Kumon H., Huh Nam-ho.
    • Journal Title

      Cancer Research 65(21)

      Pages: 9617-9622

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Adeno-Associated Virus 2-Mediated intratumoral prostate cancer gene therapy : Long-term maspin expression efficiently suppresses tumor growth.2005

    • Author(s)
      Watanabe M., Nasu Y., Kashiwakura Y., Kusumi N., Tamayose K., Nagai A., Sasano T., Shimada T., Daida H., Kumon H.
    • Journal Title

      Human Gene Therapy 16

      Pages: 699-710

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] 前立腺癌の遺伝子治療2005

    • Author(s)
      那須保友, 公文裕巳
    • Journal Title

      日本臨床 63

      Pages: 335-338

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Adenovirus-mediated overexpression of REIC/Dkk-3 selectively induces apoptosis in human prostate cancer cells through activation of JNK.2005

    • Author(s)
      F.Abarzua, Y.Nasu, H.Kumon et al.
    • Journal Title

      Cancer Research 65

      Pages: 9617-9622

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Adeno-Associated Virus-Mediated Human IL-10 Gene Transfer Suppresses the Development of Experimental Autoimmune Orchitis2005

    • Author(s)
      M.Watanabe, Y.Kashiwakura et al.
    • Journal Title

      Gene Thearpy 12

      Pages: 1126-1132

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Adeno-Associated Virus 2-Mediated Intratumoral Prostate Cancer Gene Therapy : Long-Term Maspin Expression Efficiently Suppresses Tumor Growth2005

    • Author(s)
      M.Watanabe, Y.Nasu, H.Kumon et al.
    • Journal Title

      Human Gene Therapy 16

      Pages: 699-710

    • Related Report
      2005 Annual Research Report
  • [Journal Article] 前立腺癌の遺伝子治療2005

    • Author(s)
      那須保友, 公文裕巳
    • Journal Title

      日本臨床 63(2)

      Pages: 335-338

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Interleukin-12による前立腺癌に対する新しい遺伝子治療の試み2004

    • Author(s)
      那須保友, 江原 伸, 公文裕巳
    • Journal Title

      日本臨床 62(6)

      Pages: 1181-1191

    • Related Report
      2004 Annual Research Report
  • [Journal Article] NY-ESO-1 mRNA expression and immunogenicity in advanced prostate cancer.2003

    • Author(s)
      Nakada T., Kumon H.
    • Journal Title

      Cancer Immunity 3

      Pages: 10-21

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] NY-ESO-1 mRNA expression and immunogenicity in advanced prostate cancer.2003

    • Author(s)
      Nakada T., Noguchi Y., Satoh S., Ono T., Saika T., Kurashige T., Gnjatic S., Ritter G., Chen Y-T., Stockert E., Nasu Y., Tsushima T., Kumon H., Old L.J., Nakayama E.
    • Journal Title

      Cancer Immunity 3

      Pages: 10-21

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Adeno-Associated Virus-Mediated Human IL-10 Gene Transfer Suppresses the Development of Experimental Autoimmune Orchitis

    • Author(s)
      M.Watanabe, Y Kashiwakural, et al.
    • Journal Title

      Gene Thearpy (in press)

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Adeno-Associated Virus 2-Mediated Intratumoral Prostate Cancer Gene Therapy : Long-Term Maspin Expression Efficiently Suppresses Tumor Growth

    • Author(s)
      M.Watanabe, Y.Nasu, H.Kumon
    • Journal Title

      Human Gene Therapy (in press)

    • Related Report
      2004 Annual Research Report
  • [Publications] 江原 伸, 那須保友: "前立腺癌に対する自殺遺伝子治療の最新知見"日本臨牀. 61(7). 1257-1265 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] K.Kurose, Y.Nasu, H.Kumon et al.: "Decreased Expression of REIC/Dkk-3 in Human Renal Clear Cell Carcinoma"Jouranal of Urology. 171. 1314-1318 (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] T.Nakada, Y.Nasu, H.Kumon: "NY-ESO-1 mRNA expression and immunogenicity in advanced prostate cancer."Cancer Immunity. 3. 10-15 (2003)

    • Related Report
      2003 Annual Research Report

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Published: 2003-04-01   Modified: 2016-04-21  

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