Development of Novel Therapeutic Strategy for Cancer: Targeting Cell Surface Glycan Using Endogenous Lectin-Drug Conjugate (LDC)

2019 Fiscal Year Final Research Report

• Project/Area Number: 17K10687
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Digestive surgery
• Research Institution: University of Tsukuba
• Principal Investigator: Enomoto Tsuyoshi 筑波大学, 医学医療系, 講師 (10628762)
• Co-Investigator(Kenkyū-buntansha): 小田 竜也 筑波大学, 医学医療系, 教授 (20282353)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: レクチン / 糖鎖 / 膵癌 / 胃癌 / 大腸癌

Outline of Final Research Achievements

The outermost coatings of cancer cells are composed of cell-specific glycan layers (glycocalyx).Lectins, proteins with glycan-binding potential, were evaluated for possible use as drug carriers in treatment of gastrointestinal malignancy. We constructed a tissue array using surgical specimens of gastrointestinal malignant tumor, labeled multiple endogenous lectins, and studied expression pattern of malignant tumors by organ by comprehensive lectin staining.
By the analysis of lectin staining using the tissue array of multiple carcinomas created in this study, we were able to identify lectins A and B that react specifically with tumor cells of gastric cancer and colon cancer.We are further analyzing these and are currently adjusting the drug fusion drug (Lectin-Drug conjugate), and would show the concept of utilizing lectins as drug carriers to target glycans on the cancer cell surface, highlighting new insights into cancer treatments.

Free Research Field

消化器悪性腫瘍

Academic Significance and Societal Importance of the Research Achievements

様々な分子標的治療薬が開発されているが特異度の面で十分とはいえず、未だ手術を凌駕する薬剤は開発されていない。本研究はヒト由来の内因性レクチンの中から消化器悪性腫瘍表面糖鎖を特異的に認識する内在性レクチンを選定した。一方で正常組織の反応性も高く、内因性レクチンを改変せずに薬剤の担体としても用いることは困難であることも示唆した。
今後、レクチンの薬剤送達キャリアとしての高い能力による新たなDrug Delivery法によるがん治療戦略の基盤を形成する研究である。