Development and analysis of cancer-specific monoclonal antibodies for glycoproteins

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K07705
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 50020:Tumor diagnostics and therapeutics-related
• Research Institution: Tohoku University
• Principal Investigator: KATO Yukinari 東北大学, 医学系研究科, 教授 (00571811)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: モノクローナル抗体 / がん特異的抗体 / FACS / 免疫染色 / ADCC / CDC / 抗腫瘍効果 / コアフコース欠損抗体

Outline of Final Research Achievements

EGFR contributes to tumor malignancy via gene amplification and protein overexpression. Previously, we developed an anti-human EGFR (hEGFR) monoclonal antibody, namely, EMab-134, which detects hEGFR and dog EGFR (dEGFR) with high sensitivity and specificity. In this study, we produced a defucosylated mouse-dog chimeric anti-EGFR monoclonal antibody, namely, E134Bf. In vitro analysis revealed that E134Bf highly exerted antibody-dependent cellular cytotoxicity and complement-dependent cytotoxicity against a canine osteosarcoma cell line (D-17) and a canine fibroblastic cell line (A-72), both of which express endogenous dEGFR. Moreover, in vivo administration of E134Bf significantly suppressed the development of D-17 and A-72 compared with the control dog IgG in mouse xenografts. These results indicate that E134Bf exerts antitumor effects against dEGFR-expressing canine cancers and could be valuable as part of an antibody treatment regimen for dogs.

Free Research Field

腫瘍生物学

Academic Significance and Societal Importance of the Research Achievements

EGFRに対する抗体医薬は複数開発されているが、その副作用により患者さんのQOLが良くない。我々が開発したCasMab法は、複数のタンパク質に対してがん特異的抗体の作製に成功してきた。今回、EGFRに対する抗体作製を実施した結果、EMab-134という特異的抗体の作製に成功した。また、イヌ腫瘍のマウス移植片モデルにおいて、EMab-134のイヌ化抗体よる高い抗腫瘍効果が得られた。今後、獣医師と共同で、イヌ腫瘍の治療法の開発および臨床試験を行う。さらに、ヒトEGFR高発現がんに対する治療法への応用へと発展させる。