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2001 Fiscal Year Final Research Report Summary

CLINICAL APPLICATION OF GENE THERAPY FOR UROLOGICAL MALIGNANCIES

Research Project

Project/Area Number 11307030
Research Category

Grant-in-Aid for Scientific Research (A)

Allocation TypeSingle-year Grants
Section一般
Research Field Urology
Research InstitutionTHE UNIVERSITY OF TOKYO

Principal Investigator

KITAMURA Tadaichi  The University of Tokyo, Faculty of Medicin, PROFESSOR, 医学部附属病院, 教授 (70010551)

Co-Investigator(Kenkyū-buntansha) TAKAHARA Shiro  The University of Osaka, Faculty of Medicin, Associate PROFESSOR, 大学院・医学系研究科, 助教授 (70179547)
OKUYAMA Akihiko  The University of Osaka, Faculty of Medicin, PROFESSOR, 大学院・医学系研究科, 教授 (20093388)
HORIE Shigeo  The University of Tokyo, Faculty of Medicin, Lecturer, 医学部附属病院, 講師 (40190243)
NONOMURA Norio  The University of Osaka, Faculty of Medicin, Lecturer, 大学院・医学系研究科, 講師 (30263263)
Project Period (FY) 1999 – 2001
Keywordsdendritic cells / gene therapy / HGF / urological malignacies
Research Abstract

The aim of this study was to develop and promote the clinical application of gene therapy for the urologicall malignancies. We performed research on the gene therapy of HGF gene onto animal disease model in vivo, and the induction of tumor-specific immune response by dendritic cells.
Dendritic cells (DCs) are the most potent antigen-presenting cells and induce host antitumor immunity through the T-cell response. We performed a clinical study of immunotherapy using cultured DCs loaded with tumor antigen for patients with metastatic renal cell carcinoma (RCC). DCs were generated by culturing monocytes from peripheral blood for 7 days in the presence of granulocyte-macrophage colony-stimulating factor and interleukin-4. On day 6, the DCs were pulsed with lysate from autologous tumor as the antigen and with keyhole limpet hemocyanin (KLH) as immunomodulator. The patients were given four doses of lysate-puised DCs by intradermal injection with a 2-week interval between doses. Clinical effect and immune response were respectively evaluated by radiological examination and delayed-type hypersensitivity (DTH) test. Four patients were enrolled and the immnunotherapy was well tolerated without significant toxicity. The vaccination induced a positive DTH reaction to tumor lysate in two patients and to KLH in all patients. We did not see the significant reduction of tumor volume in any case. DC vaccination can safely induce an immunological response against RCC. HGFcDNA was introduced to the rat ischemic kidney by electroporations. HGF-treated kidney developed less injury by hypoxia than controls. This experimental model was considered to be a good clinical treatment model of gene therapy renal disease

  • Research Products

    (8 results)

All Other

All Publications (8 results)

  • [Publications] TAKESHI AZUMA, SHIGEO HORIE, et al.: "Dendritic cell immunotherapy for patients with metastatic renal cell carcinoma"International Journal of Urology. 9. 340-346 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] F Xue, T Takahara, et al.: "Attenuated Acute liver injury in mice by naked hepatocyte growth factor gene transfer into skeletal muscle with electroporation"GUT. 50. 558-562 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] M KITAMURA, N TSUBONIWA et al.: "Gene therapy of ischemic damaged kidney in the rat using hepatocyte growth factor gene"Transplantation Proceedings. 33. 2865-2867 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Toshiyuki Tanaka, N Ichimaru et al.: "In vivo gene transfer of hepatocyte growth factor to skeletal muscle prevents changes in rat kidneys after 5/6 nephrectomy"American Journal of Transplantation. 2. 828-836 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Azuma T, et al.: "Dendritic cell Immunotherapy for patients with metastatic renal cell carcinoma; University of Tokyo expendence"Int J Urol.. 9(6). 340-346 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kitamura M, et al.: "Gene therapy of ischemic-damaged kidney in the rat using hepatocyte growth factor gene"Transplant Proc.. 33(5). 2865-2867 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Tanaka T, et al.: "In vivo gene transfer of hepatocyte growth factor to skeletal muscle prevents changes in rat kidnyes after 5/6 nephrectomy"Am J Transplant.. 2(9). 828-836 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] T Takahara, et al.: "Attenuated Acuteliver njury in mice by naked hepatocyte growth factor gene transfor"GOT. 50. 558-562 (2002)

    • Description
      「研究成果報告書概要(欧文)」より

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Published: 2004-04-14  

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