Glycan targeting cancer therapy; targeting cancer cell surface glycan by using a lectin as a drug carrier.

2017 Fiscal Year Final Research Report

• Project/Area Number: 16K15605
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Digestive surgery
• Research Institution: University of Tsukuba
• Principal Investigator: ODA Tatsuya 筑波大学, 医学医療系, 教授 (20282353)
• Co-Investigator(Renkei-kenkyūsha): TATENO Hiroaki 国立研究開発法人産業技術総合研究所, 創薬基盤研究部門, 主任研究員 (30450670) ; HIRABAYASHI Jun 国立研究開発法人産業技術総合研究所, 幹細胞工学研究センター・糖鎖レクチン工学研究チーム, 首席研究員・研究チーム長 (40156691) ; OHKOHCHI Nobuhiro 筑波大学, 医学医療系, 教授 (40213673) ; HASHIMOTO Shinji 筑波大学, 医学医療系, 講師 (60624666)
• Project Period (FY): 2016-04-01 – 2018-03-31
• Keywords: 膵癌 / 糖鎖 / レクチン / 腹膜播種 / 癌幹細胞 / ドラッグデリバリー / 薬剤担体 / トキシン

Outline of Final Research Achievements

Because 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 PDAC treatment. A human PDAC cell line was subjected to lectin microarray analysis to identify specific lectin-glycan pairs. The selected lectin was fused with a bacterial exotoxin for the construction of a lectin-drug conjugate (LDC), and its safety and anti-tumour effects were evaluated. A specific affinity between rBC2LC-N lecin and pancreatic cancer was identified. The IC50 of LDC 1.04 fmol/l was 1/1000 lower than that reported for immunotoxins. The intraperitoneal administration of LDC reduced the tumour weight, and reduced the number of nodules from 48 to 3 (P<0.001) and improved survival from 62 to 105 days. Herein, we 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

がん標的治療