ER2, a novel human anti-EGFR monoclonal antibody inhibit tumor activity in non-small cell lung cancer models. (May 2016)

• Record Type: Journal Article
• Authors: Kang, Han Na; Kim, Se-Ho; Yun, Mi Ran; Kim, Hye Ryun; Lim, Sun Min; Kim, Min-Soo; Hong, Kwang-Won; Kim, Sung-Moo; Kim, Hwan; Pyo, Kyoung-Ho; Park, Hye Ji; Han, Joo Yeun; Youn, Hyun A; Chang, Ki-Hwan; Cho, Byoung Chul
• Is Part Of: Lung cancer. Volume 95(2016)
• Page Start: 57
• Page End: 64
• Publication Date: 2016-05
• Subjects: ER2 -- Epidermal growth factor receptor -- Monoclonal antibody -- Non-small cell lung cancer -- Cetuximab; Lungs -- Cancer -- Periodicals; Lung Neoplasms -- Abstracts; Lung Neoplasms -- Periodicals; Poumons -- Cancer -- Périodiques; Lungs -- Cancer; Periodicals; Electronic journals; Electronic journals; 616.99424
• DOI: 10.1016/j.lungcan.2016.02.013
• Languages: English
• ISSNs: 0169-5002

Abstract

Highlights: ER2 suppressed EGFR pathway and induced G1 arrest and apoptosis in NSCLC cells. ER2 inhibited EGF-stimulated VEGF production. ER2 induced anti-tumor activity in combination with cisplatin in xenograft models. Abstract: Objectives: The epidermal growth factor receptor (EGFR) abnormalities including amplification, mutation, and overexpression are frequent in non-small cell lung cancer (NSCLC). We investigated in vitro and in vivo antitumor activity of ER2, a novel human anti-EGFR monoclonal antibody, in NSCLC. Methods: A panel of NSCLC cell lines (A549, H460, H322, H358, H1299, HCC827, PC9, H1975, and PC9-GR) was used to evaluate in vitro antitumor activity of ER2 and cetuximab. The inhibitory effects of ER2 and cetuximab on downstream signaling were assessed by western blot. Secreted VEGF was measured by Human VEGF Quantikine ELISA kit. Antitumor effects of ER2 and cetuximab as single agents and in combination with cisplatin were evaluated in H322, HCC827 and A549 xenograft models. Results: ER2 efficiently inhibits EGFR and its downstream signaling molecules including Akt and Erk1/2 in NSCLC cell lines with wild-type or mutant EGFR. ER2 inhibited cell viability of H322, HCC827 and A549 cells in a dose-dependent manner by inducing cell cycle arrest and apoptosis. Also, ER2 suppressed EGF-stimulated VEGF production as efficiently as cetuximab in H322, HCC827 and A549 cells. Moreover, ER2 alone and in combination with cisplatin showed a significant anti-tumor efficacy in xenograft mouse models. Conclusion: Taken together, ER2 has significant anti-tumor activity in in vitro and in vivo NSCLC models, suggesting a rationale for clinical development of ER2 in NSCLC.