| Project/Area Number |
25350555
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Biomedical engineering/Biomaterial science and engineering
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| Research Institution | Osaka Prefecture University (2014-2015)
Otsuma Women's University (2013) |
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Principal Investigator |
Koyama Yoshiyuki 大阪府立大学, 生命環境科学研究科(系), 客員研究員 (00162090)
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| Co-Investigator(Renkei-kenkyūsha) |
Yoshihara Chieko 大妻女子大学, 家政学部, 助手 (40597093)
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| Project Period (FY) |
2013-04-01 – 2016-03-31
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| Project Status |
Completed (Fiscal Year 2015)
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| Budget Amount *help |
¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2014: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2013: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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| Keywords | 遺伝子治療 / DNAワクチン / 結核菌抗原 / ネオアンティジェン / ネオエピトープ / 抗腫瘍ワクチン / 遺伝子導入 / プラスミド / 免疫治療 / プラスミドDNA / 抗腫瘍効果 / ESAT-6 / Ag85B / デンジャーシグナル / 癌免疫療法 / サイトカイン / DNA複合体 / 結核菌タンパク / 非ウィルスベクター / 抗腫瘍免疫 |
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| Outline of Final Research Achievements |
For an efficient tumor immunotherapy, mutant neoantigen is required as a target of immune response. We have developed a novel strategy to enhance the antitumor immune response by transfecting the pathogenic microorganism's gene into the tumor cells. It would induce the pathogenic antigen as an "artificial neoantigen" into the tumor cell surfaces, which would be recognized by antigen-presenting cells (APCs) as a "danger signal", and the immune systems would be stimulated.
Here, we employed Mycobacterium tuberculosis antigen ESAT-6 and Ag85B, as danger signal antigens. DNA complexes with ESAT-6- or Ag85B-coding plasmid demonstrated higher anti-tumor effect than those coding cytokine genes such as GM-CSF, or IL12. Co-transfection of the cytokine-genes with the pathogenic antigen genes exhibited good synergistic effect in tumor-bearing mice. Animal clinical study on primary tumor-bearing dogs was also carried out, and a significant a significant reduction of tumor volume was observed.
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