2001 Fiscal Year Final Research Report Summary
CLINICAL APPLICATION OF GENE THERAPY FOR UROLOGICAL MALIGNANCIES
| Project/Area Number |
11307030
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| Research Category |
Grant-in-Aid for Scientific Research (A)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Urology
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| Research Institution | THE UNIVERSITY OF TOKYO |
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Principal Investigator |
KITAMURA Tadaichi The University of Tokyo, Faculty of Medicin, PROFESSOR, 医学部附属病院, 教授 (70010551)
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| 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)
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| Project Period (FY) |
1999 – 2001
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| Keywords | dendritic cells / gene therapy / HGF / urological malignacies |
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| 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
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