2002 Fiscal Year Final Research Report Summary
Development of novel immunotherapy for advanced renal cell carcinoma
| Project/Area Number |
13470334
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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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 Tokushima |
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Principal Investigator |
KAGAWA Susumu The University of Tokushima, School of Medicine, Professor, 医学部, 教授 (40035738)
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| Co-Investigator(Kenkyū-buntansha) |
NISHITANI Masa-aki The University of Tokushima, University Hospital, Lecturer, 医学部附属病院, 講師 (40304521)
KANAYAMA Hiro-omi The University of Tokushima, School of Medicine, Associate Professor, 医学部, 助教授 (10214446)
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| Project Period (FY) |
2001 – 2002
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| Keywords | Renal cell carcinoma / Dendritic cell (DC) / hemiallogeneic DC / Cancer vaccine therapy / cytokine gene therapy / Interleukin-12 |
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| Research Abstract |
Advanced cases in renal cell carcinoma (RCC) have poor prognosis because of their resistance to radiation or chemotherapy. Alternative new immunotherapies for RCC are expected because of its relatively high immunogenicity. We studied the following treatments using murine models.
A cancer vaccine therapy with in vivo transfer of interleukin 12 expression plasmid
We studied combination treatment with intradermal inoculation of irradiated cancer cells and transfection with IL-12 gene using gene gun. This combination treatment inhibited tumor establishment at a distant site with enhancement of CTL and tumor inflitration by CD4+ and CD8+T cells. Our approach is safer and more convenient than vaccination with cytokine gene-transfected tumor cells.
Suppression of tumor growth by expression of angiostatin cDNA in a murine renal cell carcinoma in vivo
Angiostatin expression plasmid was constructed and introduced into Renca cells by lipofection. We showed that implantation of angiostatin-transfected cells inhibited the growth of parental Renca implanted simultaneously at a distant site via antiangiogenic effect. However, this treatment unfortunately did not exhibit the synergistic effect with interleukin 12 gene therapy.
Treatment with hemiallogeneic dendritic cell (DC)
We studied the antitumor effect of hemiallogeneic DC. We confirmed that hemiallogeneic DC had higher antitumor activity than syngeneic DC and allogeneic DC. This antitumor effect was inhibited by CD4+ T cells. These results suggest that treatment with hemiallogeneic DC will be a more effective immunotherapy for RCC.
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