Improvement of efficiency and safety of solid cancer selective anticancer molecule production system using Bifidobacterium
| Project/Area Number |
18K06781
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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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| Review Section |
Basic Section 47060:Clinical pharmacy-related
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| Research Institution | Shinshu University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
肥田 重明 名古屋市立大学, 医薬学総合研究院(薬学), 教授 (10345762)
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| Project Period (FY) |
2018-04-01 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2020)
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| Budget Amount *help |
¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000)
Fiscal Year 2020: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
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| Keywords | 固形がん / 腫瘍微小環境 / 低酸素 / DDS / ビフィズス菌 / 抗腫瘍性抗体医薬 / がん分子標的薬 / がん化学療法 / 自然免疫 / ビフィズス菌分泌蛋白質 / 免疫活性化 / 腫瘍 / 宿主免疫応答 / サイトカイン産生 / 黄色ブドウ球菌 / マクロファージ / 好中球 / TLR２,4 / 大腸菌 / 生物製剤 / 安全性 / がん治療 / 獲得免疫 / サイトカイン / 抗がん分子 / デリバリー |
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| Outline of Final Research Achievements |
In the clinical application of DDS using bifidobacterium (B), we investigated the immune response against B using macrophages and dendritic cells to create an immune safety basis. B induced the production of cytokines such as IL-6 and TNF-α, and we found the reaction was caused through TLR2. On the other hand, in killed B, cytokine production and anti-B IgG antibody production were significantly reduced. Some polysaccharides and proteins on the wall of B were identified as candidates for involvement in immune activation. An expression system for cytokines and svFc was established with B, and the combined use of anti-PD1 antibody and cytosine deaminase-producing B / 5F C was observed to suppress tumor growth and enhance the survival.
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| Academic Significance and Societal Importance of the Research Achievements |
がん分子標的薬は、特定がんに対し効果を示し、副作用も減少するが、薬剤耐性細胞出現が懸念材料である。また抗体医薬等の有効性は、数多く報告されているが、その薬価は高額で自己免疫疾患的な副反応が深刻な場合が報告されている。蛋白質製剤は、その製造コストが高く、高薬価となる。副作用に関しても分子標的が腫瘍非特異的で、全身投与では副反応が生じる。これらの問題点を改善するために、固形がんの低酸素微小環境に着目し、ビフィズス菌による抗体医薬の腫瘍局所での持続的発現・分泌系の樹立は、比較的安価で低副作用の医薬品を開発できる。さらに副作用の問題で開発が断念された医薬品についても、利用できる可能性がある。
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Report
(4 results)
Research Products
(15 results)
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[Journal Article] IL-1β Plays an Important Role in Pressure Overload-Induced Atrial Fibrillation in Mice2019
Author(s)
Matsushita N, Ishida N, Ibi M, Saito M, Takahashi M, Taniguchi S, Iwakura Y, Morino Y, Taira E, Sawa Y, Hirose M
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Journal Title
Biological and Pharmaceutical Bulletin
Volume: 42
Issue: 4
Pages: 543-546
DOI
NAID
ISSN
0918-6158, 1347-5215
Year and Date
2019-04-01
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Potential Role of ASC, a Proapoptotic Protein, for Determining the Cisplatin Susceptibility of Lung Cancer Cells2018
Author(s)
Takao Sakaizawa, Tomio Matsumura, Chifumi Fujii, Shigeaki Hida, Masayuki Toishi, Takayuki Shiina, Kazuo Yoshida, Kazutoshi Hamanaka, Ken-ichi Ito and Shun’ichiro Taniguchi
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Journal Title
The Tohoku Journal of Experimental Medicine
Volume: 244
Issue: 2
Pages: 133-144
DOI
NAID
ISSN
0040-8727, 1349-3329
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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