2. Academic Validation
  3. GC1118, an Anti-EGFR Antibody with a Distinct Binding Epitope and Superior Inhibitory Activity against High-Affinity EGFR Ligands

GC1118, an Anti-EGFR Antibody with a Distinct Binding Epitope and Superior Inhibitory Activity against High-Affinity EGFR Ligands

  • Mol Cancer Ther. 2016 Feb;15(2):251-63. doi: 10.1158/1535-7163.MCT-15-0679.
Yangmi Lim 1,  Jiho Yoo 2,  Min-Soo Kim 1,  Minkyu Hur 3,  Eun Hee Lee 1,  Hyung-Suk Hur 1,  Jae-Chul Lee 1,  Shi-Nai Lee 1,  Tae Wook Park 1,  Kyuhyun Lee 1,  Ki Hwan Chang 1,  Kuglae Kim 2,  YingJin Kang 2,  Kwang-Won Hong 1,  Se-Ho Kim 4,  Yeon-Gil Kim 5,  Yeup Yoon 6,  Do-Hyun Nam 7,  Heekyoung Yang 8,  Dong Geon Kim 9,  Hyun-Soo Cho 10,  Jonghwa Won 11
Affiliations

Affiliations

  • 1 MOGAM Biotechnology Institute, Yongin, Gyeonggi-do, Republic of Korea.
  • 2 Department of Systems Biology, College of Life Science and Biotechnology, Yonsei University, Seoul, Republic of Korea.
  • 3 MOGAM Biotechnology Institute, Yongin, Gyeonggi-do, Republic of Korea. Graduate School of Medicine, Korea University College of Medicine, Korea University, Seoul, Republic of Korea.
  • 4 University-Industry Cooperation Foundation, and Department of Systems Immunology, College of Biomedical Science, Kangwon National University, Chuncheon, Kangwon-Do, Republic of Korea.
  • 5 Pohang Accelerator Laboratory, Pohang University of Science and Technology, Pohang, Kyungbuk, Republic of Korea.
  • 6 Institute for Refractory Cancer Research, Samsung Medical Center, Seoul, Republic of Korea. Samsung Biomedical Research Institute, Samsung Medical Center, Seoul, Republic of Korea. Department of Health Sciences and Technology, SAIHST, Sungkyunkwan University, Seoul, Republic of Korea.
  • 7 Institute for Refractory Cancer Research, Samsung Medical Center, Seoul, Republic of Korea. Samsung Biomedical Research Institute, Samsung Medical Center, Seoul, Republic of Korea. Department of Health Sciences and Technology, SAIHST, Sungkyunkwan University, Seoul, Republic of Korea. Samsung Medical Center, School of Medicine, Sungkyunkwan University, Seoul, Republic of Korea.
  • 8 Institute for Refractory Cancer Research, Samsung Medical Center, Seoul, Republic of Korea. Samsung Biomedical Research Institute, Samsung Medical Center, Seoul, Republic of Korea. Samsung Medical Center, School of Medicine, Sungkyunkwan University, Seoul, Republic of Korea.
  • 9 Institute for Refractory Cancer Research, Samsung Medical Center, Seoul, Republic of Korea. Department of Health Sciences and Technology, SAIHST, Sungkyunkwan University, Seoul, Republic of Korea.
  • 10 Department of Systems Biology, College of Life Science and Biotechnology, Yonsei University, Seoul, Republic of Korea. agnes@mogam.re.kr hscho8@yonsei.ac.kr.
  • 11 MOGAM Biotechnology Institute, Yongin, Gyeonggi-do, Republic of Korea. agnes@mogam.re.kr hscho8@yonsei.ac.kr.
PMID: 26586721 DOI: 10.1158/1535-7163.MCT-15-0679
Abstract

The EGFR-targeted monoclonal antibodies are a valid therapeutic strategy for patients with metastatic colorectal Cancer (mCRC). However, only a small subset of mCRC patients has therapeutic benefits and there are high demands for EGFR therapeutics with a broader patient pool and more potent efficacy. In this study, we report GC1118 exhibiting a different character in terms of binding epitope, affinity, mode of action, and efficacy from Other anti-EGFR antibodies. Structural analysis of the EGFR-GC1118 crystal complex revealed that GC1118 recognizes linear, discrete N-terminal epitopes of domain III of EGFR, critical for EGF binding but not overlapping with those of Other EGFR-targeted antibodies. GC1118 exhibited superior inhibitory activity against high-affinity EGFR ligands in terms of EGFR binding, triggering EGFR signaling, and proliferation compared with cetuximab and panitumumab. EGFR signaling driven by low-affinity ligands, on the contrary, was well inhibited by all the antibodies tested. GC1118 demonstrated robust antitumor activity in tumor xenografts with elevated expression of high-affinity ligands in vivo, whereas cetuximab did not. Considering the significant role of high-affinity EGFR ligands in modulating tumor microenvironment and inducing resistance to various Cancer therapeutics, our study suggests a potential therapeutic advantage of GC1118 in terms of efficacy and a range of benefited patient pool. Mol Cancer Ther; 15(2); 251-63. ©2015 AACR.

Figures
Products
  • Cat. No.
    Product Name
    Description
    Target
    Research Area
  • HY-P991571
    EGFR Monoclonal Antibody