| Project/Area Number |
13671422
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Cerebral neurosurgery
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| Research Institution | Chiba University |
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Principal Investigator |
IWADATE Yasuo Chiba University, Graduate School of Medicine, Assistant, 大学院・医学研究院, 助手 (70272309)
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| Co-Investigator(Kenkyū-buntansha) |
YAMAURA Akira Chiba University, Graduate School of Medicine, Professor, 大学院・医学研究院, 教授 (40009717)
SAEKI Naokatsu Chiba University, Graduate School of Medicine, Associate Professor, 大学院・医学研究院, 助教授 (30143275)
TAGAWA Masatoshi Chiba Cancer Center, DIVISION CHIEF, 病理研究部, 部長 (20171572)
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| Project Period (FY) |
2001 – 2002
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| Project Status |
Completed (Fiscal Year 2002)
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| Budget Amount *help |
¥3,100,000 (Direct Cost: ¥3,100,000)
Fiscal Year 2002: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 2001: ¥1,800,000 (Direct Cost: ¥1,800,000)
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| Keywords | Glioma / Cytokine / immune gene therapy / neural progenitor cell / Interleukin-2 / Brain Neoplasm / Gene Therapy / Antitamor Immunity / Neural Progenitor Cell / IL-2 / IL-4 / GM-CSF |
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| Research Abstract |
Cytokine gene therapy for the central nervous system tumors has proven to have significant potential, but it needs improvement in the process of antigen presentation and/or in insufficient recruitment of immunocompetent cells to achieve successful eradication of established brain tumors. We investigated the therapeutic potential of induced systemic immunity in peripheral tissues combined with the production of various cytokines in the vicinity of brain tumors to treat established brain tumors. Sequential magneti resonance image (MRI) monitoring showed that the combinatory therapy consisting of intracerebral (i.c.) transplantation of IL-2-producing syngeneic or xenogeneic cells and subcutaneous (s.c.) vaccination using irradiated 9L or 9L/IL-2 cells could cured 9L-bearing rats, whereas either the i.c. injection of IL-2-producers or the s.c. vaccination alone produced little or marginal anti-tumor effects, respectively. Other cytokines such as IL-4, IL-12, or GM-CSF could not induce sign
… More
ificant therapeutic effects against the established brain tumors. Glioma-specific CTL activity was equivalently induced in the rats vaccinated s.c. with irradiated 9L, irradiated IL-2-producing 9L cells or the mixed population of irradiated 9L and C1300/IL-2 cells, while the activity was relatively lower in the rats vaccinated with irradiated 9L cells mixed with either C1300/IL-4 or C1300/GM-CSF cells. In the rats immunized s.c. with irradiated 9L cells, i.c. 9L tumors implanted together with either C1300/IL-2 or C1300/IL-4 were completely rejected. Pre-established brain tumor also could be eliminated by the s.c. immunization of irradiated 9L cells and i.c. transplantation of IL-2-producers. Immunohistochemical analysis revealed that a number of CD4^+ and CD8^+ T cells infiltrated into the brain tumors which were treated with the combinatory therapy. The level of cell infiltration was similar to that found in s.c. 9L/IL-2 tumors which were subsequently rejected. These results suggest that glioma-specific CTLs could be effectively induced by s.c. immunization of irradiated wild-type tumor cells without artificial cytokine production. The combinatory strategy, i.c. grafting of IL-2-producing cells and s.c. immunization of irradiated whole tumor cell vaccine, is thus effective for recruiting activated T cells into the brain tumor site and could be a potential therapy for brain tumors. Less
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