Lectin drug conjugate therapy for colorectal cancer

Research Project

Project/Area Number	20K16404
Research Category	Grant-in-Aid for Early-Career Scientists
Allocation Type	Multi-year Fund
Review Section	Basic Section 50020:Tumor diagnostics and therapeutics-related
Research Institution	University of Tsukuba
Principal Investigator	Ohara Yusuke 筑波大学, 医学医療系, 講師 (90757791)
Project Period (FY)	2020-04-01 – 2024-03-31
Project Status	Completed (Fiscal Year 2023)
Budget Amount *help	¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000) Fiscal Year 2023: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000) Fiscal Year 2022: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000) Fiscal Year 2021: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000) Fiscal Year 2020: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Keywords	レクチン / 糖鎖 / 大腸癌 / 抗がん治療 / マイクロアレイ
Outline of Research at the Start	所属研究室ではレクチンマイクロアレイ技術、臨床に即した動物モデルを駆使して膵癌特異的糖鎖を同定し（H-Type 1/3/4）、特異的に結合するレクチンrBC2LC-N を発見した。レクチンとエンドトキシンの融合薬を作製し、マウス膵癌モデルにて著しい抗腫瘍効果を認めた。この膵癌に対する成果をもとに、現在レクチン創薬に向けて準備しているが、膵癌よりも罹患率が高い大腸癌への適応を視野に入れている。本研究では大腸癌における糖鎖発現、マウスでの抗腫瘍効果の確認、薬理動態の解明を行い、本研究室が推進する創薬を大腸癌へ応用するための基盤となる実験を行う。
Outline of Final Research Achievements	Our laboratory has identified pancreatic cancer-specific glycans (H-Type 1/3/4) using lectin microarray technology and clinically relevant animal models, and discovered a lectin, rBC2LC-N, which binds specifically to these glycans. We produced a fusion drug of lectin and endotoxin, which showed remarkable anti-tumor effects in a mouse pancreatic cancer model. Based on the results for pancreatic cancer, we are now preparing for lectin drug discovery, and have conducted research with a view to its application to colorectal cancer, which has a higher incidence than pancreatic cancer. In this study, we conducted experiments to elucidate glycan expression in colorectal cancer, to confirm its antitumor effect in mice, and to elucidate its pharmacokinetics, which will serve as a basis for the application of drug discovery to colorectal cancer, which our laboratory is promoting.
Academic Significance and Societal Importance of the Research Achievements	本課題においては、糖鎖、レクチンをターゲットとした新規大腸癌治療戦略における基礎的研究の成果を得ることができた。これらにより本コンセプトが十分に臨床応用可能な治療になりうることを示すことができたと考える。