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Novel cancer therapy strategies, targeting cancer cell surface glycans using lectins (=glycan binding protein) as drug carriers.

Research Project

Project/Area Number 18H04057
Research Category

Grant-in-Aid for Scientific Research (A)

Allocation TypeSingle-year Grants
Section一般
Review Section Medium-sized Section 55:Surgery of the organs maintaining homeostasis and related fields
Research InstitutionUniversity of Tsukuba

Principal Investigator

ODA Tatsuya  筑波大学, 医学医療系, 教授 (20282353)

Co-Investigator(Kenkyū-buntansha) 下村 治  筑波大学, 医学医療系, 講師 (60808070)
Project Period (FY) 2018-04-01 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥44,070,000 (Direct Cost: ¥33,900,000、Indirect Cost: ¥10,170,000)
Fiscal Year 2021: ¥10,270,000 (Direct Cost: ¥7,900,000、Indirect Cost: ¥2,370,000)
Fiscal Year 2020: ¥10,270,000 (Direct Cost: ¥7,900,000、Indirect Cost: ¥2,370,000)
Fiscal Year 2019: ¥11,180,000 (Direct Cost: ¥8,600,000、Indirect Cost: ¥2,580,000)
Fiscal Year 2018: ¥12,350,000 (Direct Cost: ¥9,500,000、Indirect Cost: ¥2,850,000)
Keywords糖鎖標的治療 / レクチン / 膵がん / 緑膿菌外毒素(PE38) / 膵癌 / 糖鎖 / 癌標的治療 / 標的治療 / がん特異的糖鎖 / 薬剤融合タンパク / がん標的治療 / rBC2LC-N
Outline of Final Research Achievements

We aimed to realize a novel cancer therapy by targeting specific glycan structures (Htype3) covering the outermost layer of pancreatic cancer cells with BC2 lectin. LDC, which is BC2 lectin conjugated with Pseudomonas aeruginosa exotoxin, showed high antitumor effect not only on pancreatic cancer but also on colon cancer and stomach cancer. Aiming for clinical application to humans, we purified a GMP-grade formulation in collaboration with a pharmaceutical company to obtain a pure trimeric LDC, but gave up the development of human application due to its strong off-target accumulation and toxicity in the kidney and liver. On the other hand, we found that the carrier protein of Htype3 on the surface of cancer cells is CEA and that BC2 lectin can be used as a modification of doxorubicin to improve its targetability and as a carrier of photoimmunomaterials, opening a new path for the clinical application of BC2 lectin.

Academic Significance and Societal Importance of the Research Achievements

癌細胞を標的する上で、最外層を覆う糖鎖層を狙う事が最も効率的であるはずだが、これまで糖鎖に焦点化した創薬研究はほとんど行われていない。まして、主に糖鎖の検出プローブとして体外利用しかされてこなかったレクチンを生体内に投与する薬剤キャリアーとして利用する試みは非常に挑戦的なものである。既存の抗体薬は動物培養細胞でしか生産出来ず非常に高価で国民医療費を大きく圧迫する経済的問題も大きい。それに対してレクチン医薬は、難治がんの代表である膵癌に対して、画期的な新規治療という医療効果が期待できるだけでなく、ポスト抗体医薬として、新しい安価ながん標的治療のプラットフォームとしての意味合いを有する。

Report

(3 results)
  • 2021 Final Research Report ( PDF )
  • 2019 Annual Research Report
  • 2018 Annual Research Report
  • Research Products

    (8 results)

All 2019 2018

All Journal Article (6 results) (of which Int'l Joint Research: 4 results,  Peer Reviewed: 4 results,  Open Access: 4 results) Presentation (2 results)

  • [Journal Article] Enhanced hepatic differentiation in the subpopulation of human amniotic stem cells under 3D multicellular microenvironment2019

    • Author(s)
      Furuya K, Zheng YW, Sako D, Iwasaki K, Zheng DX, Ge JY, Liu LP, Furuta T, Akimoto K, Yagi H, Hamada H, Isoda H, Oda T and Ohkohchi N
    • Journal Title

      World J Stem Cells

      Volume: 11 Issue: 9 Pages: 705-721

    • DOI

      10.4252/wjsc.v11.i9.705

    • NAID

      120007133054

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Recurrent renal cell carcinoma leading to a misdiagnosis of polycystic liver disease: A case report2019

    • Author(s)
      Liang Chen、Takahashi Kazuhiro、Kurata Masanao、Sakashita Shingo、Oda Tatsuya、Ohkohchi Nobuhiro
    • Journal Title

      World Journal of Gastroenterology

      Volume: 25 Issue: 18 Pages: 2264-2270

    • DOI

      10.3748/wjg.v25.i18.2264

    • NAID

      120007133496

    • Related Report
      2019 Annual Research Report
  • [Journal Article] Pathological complete response after preoperative chemotherapy including FOLFOX plus bevacizumab for locally advanced rectal cancer: A case report and literature review2019

    • Author(s)
      Miyamoto Ryoichi、Kikuchi Kazunori、Uchida Atsushi、Ozawa Masayoshi、Sano Naoki、Tadano Sosuke、Inagawa Satoshi、Oda Tatsuya、Ohkohchi Nobuhiro
    • Journal Title

      International Journal of Surgery Case Reports

      Volume: 62 Pages: 85-88

    • DOI

      10.1016/j.ijscr.2019.08.010

    • Related Report
      2019 Annual Research Report
  • [Journal Article] Retrocolic Gastrojejunostomy After Pancreaticoduodenectomy: A Satisfactory Delayed Gastric-Emptying Rate.2019

    • Author(s)
      Miyazaki Y1, Oda T, Shimomura O, Enomoto T, Akashi Y, Hisakura K, Ohara Y, Kimura S, Hashimoto S, Ohkohchi N.
    • Journal Title

      Pancreas.

      Volume: 48 Issue: 4 Pages: 579-584

    • DOI

      10.1097/mpa.0000000000001295

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Indocyanine green fluorescence-navigated laparoscopic metastasectomy for peritoneal metastasis of hepatocellular carcinoma: a case report.2018

    • Author(s)
      Miyazaki Y1, Kurata M2, Oshiro Y1, Shimomura O1, Takahashi K1, Oda T1, Ohkohchi N1.
    • Journal Title

      Surg Case Rep.

      Volume: 4 Issue: 1 Pages: 130-133

    • DOI

      10.1186/s40792-018-0537-x

    • NAID

      120007128329

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Surgical resection of hepatic and rectal metastases of pancreatic acinar cell carcinoma (PACC): a case report.2018

    • Author(s)
      Ohara Y, Oda T, Enomoto T, Hisakura K, Akashi Y, Ogawa K, Owada Y, Domoto Y, Miyazaki Y, Shimomura O, Kurata M, Ohkohchi N.
    • Journal Title

      World J Surg Oncol

      Volume: 16 Issue: 1 Pages: 1457-8

    • DOI

      10.1186/s12957-018-1457-8

    • NAID

      120007133820

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] 結合タンパク「レクチン」を用いた新規膵癌標的治療法の開発2018

    • Author(s)
      下村 治; 小田 竜也; 舘野浩章; 木村聡大; 宮崎貴寛; 小澤佑輔、大河内信弘、
    • Organizer
      第49回日本膵臓学会大会
    • Related Report
      2018 Annual Research Report
  • [Presentation] レクチン薬剤複合体を用いた膵癌細胞表面糖鎖をターゲットにした新規癌治療【Molecular Cancer Therapeutics】2018

    • Author(s)
      下村 治; 小田 竜也; 舘野浩章; 小澤佑介; 木村聡大; 坂下信悟、野口雅之、大河内信弘
    • Organizer
      第118回日本外科学会定期学術集会
    • Related Report
      2018 Annual Research Report

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Published: 2018-04-23   Modified: 2025-01-30  

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