Novel cancer therapy strategies, targeting cancer cell surface glycans using lectins (=glycan binding protein) as drug carriers.
| Project/Area Number |
18H04057
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| Research Category |
Grant-in-Aid for Scientific Research (A)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Review Section |
Medium-sized Section 55:Surgery of the organs maintaining homeostasis and related fields
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| Research Institution | University of Tsukuba |
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Principal Investigator |
ODA Tatsuya 筑波大学, 医学医療系, 教授 (20282353)
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| Co-Investigator(Kenkyū-buntansha) |
下村 治 筑波大学, 医学医療系, 講師 (60808070)
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| Project Period (FY) |
2018-04-01 – 2022-03-31
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| Project Status |
Completed (Fiscal Year 2021)
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| 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)
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| 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 / がん特異的糖鎖 / 薬剤融合タンパク / 標的治療 / がん標的治療 / rBC2LC-N |
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| 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.
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| 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。
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Report
(2 results)
Research Products
(5 results)
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[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.
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Journal Title
World J Surg Oncol
Volume: 16
Issue: 1
Pages: 1457-8
DOI
NAID
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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