American Association for Cancer Research
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Supplementary table 1 from GC1118, an Anti-EGFR Antibody with a Distinct Binding Epitope and Superior Inhibitory Activity against High-Affinity EGFR Ligands

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journal contribution
posted on 2023-04-03, 14:40 authored by Yangmi Lim, Jiho Yoo, Min-Soo Kim, Minkyu Hur, Eun Hee Lee, Hyung-Suk Hur, Jae-Chul Lee, Shi-Nai Lee, Tae Wook Park, Kyuhyun Lee, Ki Hwan Chang, Kuglae Kim, YingJin Kang, Kwang-Won Hong, Se-Ho Kim, Yeon-Gil Kim, Yeup Yoon, Do-Hyun Nam, Heekyoung Yang, Dong Geon Kim, Hyun-Soo Cho, Jonghwa Won

Supplementary Table 1. X-ray data collection and refinement statistics.


the Korea Healthcare technology R&D project, Ministry for Health & Welfare Affairs, Republic of Korea




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.