Abstract 3496: GC1118, a novel anti-EGFR andtibody, shows more potent antitumor activity regardless of KRAS mutation or high-affinity lignad stimulation compared with cetuximab in gastric cancer

Abstract

Abstract Background: EGFR overexpression in gastric cancer (GC) has been reported in about 30% of patients. However, cetuximab and panitumulab, anti-EGFR antibodies, have failed to improve overall survival of GC patients compared with standard chemotherapy alone. GC1118 is a novel anti-EGFR antibody with distinct binding epitope compared to cetuximab or panitumumab, and has superior inhibitory activity against high-affinity EGFR ligands (Mol Cancer Ther 2016). In this study, GC1118 was tested to evaluate the antitumor effects in gastric cancer cells. Methods: Using a total of 15 kinds of GC cell lines (SNU-1, SNU-5, SNU-16, SNU-216, SNU-484, SNU-601, SNU-620, SNU-638, SNU-668, SNU-719, AGS, MKN-28, MKN-45, NCI-N87, and KATO-), GC1118, cetuximab, cisplatin, and 5-FU were tested. Cells were treated with or without high-affinity EGFR ligands, EGF 20ng/mL or HB-EGF 100ng/mL. Result: GC1118 exhibited more potent antigrowth effects in the majority of GC cells than cetuximab in colony forming assay and MTT assay, regardless of KRAS mutation status of cells. The synergistic efficacy was observed when cells were treated with GC1118 in combination with cytotoxic chemotherapeutic agents (cisplatin or 5FU) in colony formation assay and migration assay compared to each treatment alone, even under the EGFR-ligand stimulation condition. GC1118 significantly blocked the p-AKT or p-ERK signaling under the presence of ligand induced-EGFR activation. However, cetuximab failed to block p-AKT or p-ERK that was upregulated by EGF or HB-EGF. Moreover, this signal-blocking activity was more potent in case of GC1118 compared with cetuximab in the chemotherapy combination experiment. Conclusion: GC1118 showed more potent antitumor effects in GC compared with cetuximab. In combination with cytotoxic chemotherapy, GC1118 also has more potent activity compared with cetuximab regardless of KRAS mutation status or high-affinity ligand stimulation condition. This study supports further clinical development of GC1118 in gastric cancer. Citation Format: Ji Eun Park, Mei Hua Jin, Ah-Rong Nam, Ju-Hee Bang, Do-Youn Oh, Yung-Jue Bang. GC1118, a novel anti-EGFR andtibody, shows more potent antitumor activity regardless of KRAS mutation or high-affinity lignad stimulation compared with cetuximab in gastric cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 3496.