Antibody-dependent cellular cytotoxicity with defucosylated monoclonal antibodies in patients with GI-tract cancer

2019 Fiscal Year Final Research Report

• Project/Area Number: 17K10597
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Digestive surgery
• Research Institution: Fukushima Medical University
• Principal Investigator: Nakajima Takahiro 福島県立医科大学, 医学部, 博士研究員 (90567447)
• Co-Investigator(Kenkyū-buntansha): 河野 浩二 福島県立医科大学, 医学部, 教授 (40283204)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: ADCC / 抗体治療 / 免疫治療

Outline of Final Research Achievements

Although herceptin and rituximab are a standard treatment for breast and gastric cancer and lymphoma, their efficacy is still limited. In this study, trastuzumab- and cetuximab-mediated ADCC by comparing defucosylated mAbs with conventional mAbs using peripheral blood mononuclear cells (PBMCs) were performed. When the defucosylated mAbs were used instead of the conventional mAbs, the ADCC activities in the advanced cancer cases were almost comparable with those in early disease or healthy individuals.In conclusion, defucosylated therapeutic mAbs can enhance ADCC activities in patients with cancer.

Free Research Field

消化器外科

Academic Significance and Societal Importance of the Research Achievements

本研究では、消化管癌において、既存の抗体医薬に比し脱フコシル化抗体の有効性を示すことを目標とし、消化器癌患者20名から末梢血リンパ球を分離し、脱フコシル化ハーセプチンと、脱フコシル化セツキシマブを用いたADCCを検討し、脱フコシル化抗体が、有意にADCCを増強させることを突き止めた。この成果は、消化器癌領域において、抗体医薬の治療効果増強に大きく寄与し、癌治療の向上に役立つ。