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Improvement of efficiency and safety of solid cancer selective anticancer molecule production system using Bifidobacterium

Research Project

Project/Area Number 18K06781
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 47060:Clinical pharmacy-related
Research InstitutionShinshu University

Principal Investigator

Taniguchi Shun'ichiro  信州大学, 医学部, 特任教授 (60117166)

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)
Project Period (FY) 2018-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
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)
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
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.

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。

Report

(4 results)
  • 2020 Annual Research Report   Final Research Report ( PDF )
  • 2019 Research-status Report
  • 2018 Research-status Report
  • Research Products

    (15 results)

All 2020 2019 2018

All Journal Article (9 results) (of which Int'l Joint Research: 6 results,  Peer Reviewed: 9 results,  Open Access: 9 results) Presentation (6 results) (of which Int'l Joint Research: 5 results)

  • [Journal Article] Potentiated antitumor effects of APS001F/5-FC combined with anti-PD-1 antibody in a CT26 syngeneic mouse model.2020

    • Author(s)
      Shioya K, Matsumura T, Seki Y, Shimizu H, Nakamura T, Taniguchi S.
    • Journal Title

      iosci Biotechnol Biochem.

      Volume: 85 Issue: 2 Pages: 324-331

    • DOI

      10.1093/bbb/zbaa057

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Short-chain fatty acids bind to apoptosis-associated speck-like protein to activate inflammasome complex to prevent Salmonella infection2020

    • Author(s)
      Tsugawa Hitoshi、Kabe Yasuaki、Kanai Ayaka、Sugiura Yuki、Hida Shigeaki、Taniguchi Shun’ichiro、Takahashi Toshio、Matsui Hidenori、Yasukawa Zenta、Itou Hiroyuki、Takubo Keiyo、Suzuki Hidekazu、Honda Kenya、Handa Hiroshi、Suematsu Makoto
    • Journal Title

      PLOS Biology

      Volume: 18 Issue: 9 Pages: 3000813-3000813

    • DOI

      10.1371/journal.pbio.3000813

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Cecal Tumorigenesis in Aryl Hydrocarbon Receptor-Deficient Mice Depends on Cecum-Specific Mitogen-Activated Protein Kinase Pathway Activation and Inflammation.2020

    • Author(s)
      Matoba H, Takamoto M, Fujii C, Kawakubo M, Kasuga E, Matsumura T, Natori T, Misawa K, Taniguchi S, Nakayama J.
    • Journal Title

      Am J Pathol.

      Volume: 190 Issue: 4 Pages: 453-468

    • DOI

      10.1038/hr.2016.158

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [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
    • Journal Title

      Biological and Pharmaceutical Bulletin

      Volume: 42 Issue: 4 Pages: 543-546

    • DOI

      10.1248/bpb.b18-00363

    • NAID

      130007622152

    • ISSN
      0918-6158, 1347-5215
    • Year and Date
      2019-04-01
    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] IL-1β Plays an Important Role in Pressure Overload-Induced Atrial2019

    • Author(s)
      N Matsushita, N Ishida, M Takahashi, S Taniguchi, Y Iwakura, Y Sawa, M Hirose et al.
    • Journal Title

      Biological and Pharmaceutical Bulletin

      Volume: 42 Pages: 543-546

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Cutting Edge: G Protein Subunit b 1 Negatively Regulates NLRP3 Inflammasome Activation2019

    • Author(s)
      Tomohiko Murakami, Lerdluck Ruengsinpinya, Eriko Nakamura,Yoshifumi Takahata, Kenji Hata, Hiroaki Okae,Shun’ichiro Taniguchi, Masafumi Takahashi and Riko Nishimura
    • Journal Title

      The Journal of Immunology

      Volume: 202 Issue: 7 Pages: 1942-1947

    • DOI

      10.4049/jimmunol.1801388

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [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
    • Journal Title

      The Tohoku Journal of Experimental Medicine

      Volume: 244 Issue: 2 Pages: 133-144

    • DOI

      10.1620/tjem.244.133

    • NAID

      130006356063

    • ISSN
      0040-8727, 1349-3329
    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Fascin1 suppresses RIG-I like receptor signaling and interferon-2018

    • Author(s)
      Tomio Matsumura Shigeaki Hida Masato Kitazawa Chifumi Fujii Akira Kobayashi Michiko Takeoka Shun'ichiro Taniguchi,and Shin-ichi Miyagawa
    • Journal Title

      J. Biol. Chem.

      Volume: 293 Issue: 17 Pages: 6326-6336

    • DOI

      10.1074/jbc.m117.819201

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] The eNOS-NO pathway attenuates kidney dysfunction via suppression of inflammasome activation in aldosterone-induced renal injury model mice2018

    • Author(s)
      Yuji Sogawa, Hajime Nagasu , Seiji Itano, Kengo Kidokoro, Shun’ichiro Taniguchi, Masafumi Takahashi, Hiroyuki Kadoya, Minoru Satoh, Tamaki Sasaki, Naoki Kashihara
    • Journal Title

      ProS One

      Volume: 13 Issue: 10 Pages: e0203823-e0203823

    • DOI

      10.1371/journal.pone.0203823

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] Enhanced Anti-tumor Effects of IFN- γ Producing Bifidobacterium in Combination with PD-1 Antibody in a Syngeneic Murine Model2019

    • Author(s)
      Satoshi KOBAYASHI , Yuji SEKI , Koichiro SHIOYA , Shiro KATAOKA , Li WANG , 1231 Yuko SHIMATANI , Minoru FUJIMORI , Shun’ichiro TANIGUCHI , Takaaki NAKAMURA
    • Organizer
      5th International Symposium for Medicinal Sciences
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] Engineered Bacterial Cancer Therapy Using Bifidobacterium Secreting Agonistic Anti-4-1BB scFv in the Mouse Model2019

    • Author(s)
      Tomio MATSUMURA , Koichiro SHIOYA , Yasuyoshi KANARI , Yuko SHIMATANI , 1211 Shiro KATAOKA , Shun’ichiro TANIGUCHI , Takaaki NAKAMURA
    • Organizer
      5th International Symposium for Medicinal Sciences
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] Immune modulation by Bifidobacteria-derived molecules2019

    • Author(s)
      Naoto Fujioka, Yuma Itoh, Shungo Sasaki, Saotomo Itoh, Shun’ichiro Taniguchi, Shigeaki Hida
    • Organizer
      日本免疫学学会
    • Related Report
      2019 Research-status Report
  • [Presentation] Engineered bacterial cancer therapy using Bifidobacterium secreting agonistic anti-4-1BB scFv in the mouse model2019

    • Author(s)
      Tomio Matsumura, Koichiro Shioya, Yasuyoshi Kanari, Yuko Shimatani, Shiro Kataoka, Shun’ichiro Taniguchi, Takaaki Nakamura
    • Organizer
      5th International Symposium for Medicinal Sciences
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] Enhanced anti-tumor effects of IFN-γ producing Bifidobacterium in combination with PD-1 antibody in a syngeneic murine model2019

    • Author(s)
      Satoshi Kobayashi, Yuji Seki, Koichiro Shioya, Shiro Kataoka, Li Wang, Yuko Shimatani, Minoru Fujimori, Shun'ichiro Taniguchi, Takaaki Nakamura1
    • Organizer
      5th International Symposium for Medicinal Sciences
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] Bifidobacterium producing interferon-γ induced tumor shrinkage in combination with anti-PD-1 blockade in syngeneic mouse model2018

    • Author(s)
      Shiro Kataoka, Satoshi Kobayashi , Yuji Seki, Koichiro Shioya, Li Wang, Yuko Shimatani, Takaaki Nakamura, Shun'ichiro Taniguchi
    • Organizer
      Keystone Symposium
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research

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Published: 2018-04-23   Modified: 2022-01-27  

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