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

 Han Na Kang  ;  Se-Ho Kim  ;  Mi Ran Yun  ;  Hye Ryun Kim  ;  Sun Min Lim  ;  Min-Soo Kim  ;  Kwang-Won Hong  ;  Sung-Moo Kim  ;  Hwan Kim  ;  Kyoung-Ho Pyo  ;  Hye Ji Park  ;  Joo Yeun Han  ;  Hyun A Youn  ;  Ki-Hwan Chang  ;  Byoung Chul Cho 
 LUNG CANCER, Vol.95 : 57-64, 2016 
Journal Title
Issue Date
Animals ; Antibodies, Monoclonal, Humanized/pharmacology* ; Antineoplastic Agents/pharmacology* ; Apoptosis/drug effects ; Carcinoma, Non-Small-Cell Lung/drug therapy ; Carcinoma, Non-Small-Cell Lung/metabolism* ; Carcinoma, Non-Small-Cell Lung/pathology* ; Cell Cycle Checkpoints/drug effects ; Cell Line, Tumor ; Cisplatin/pharmacology ; Disease Models, Animal ; Drug Synergism ; Female ; Humans ; Lung Neoplasms/drug therapy ; Lung Neoplasms/metabolism* ; Lung Neoplasms/pathology* ; Mice ; Receptor, Epidermal Growth Factor/antagonists & inhibitors* ; Receptor, Epidermal Growth Factor/metabolism ; Signal Transduction/drug effects ; Xenograft Model Antitumor Assays
Cetuximab ; ER2 ; Epidermal growth factor receptor ; Monoclonal antibody ; Non-small cell lung cancer
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.
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1. College of Medicine (의과대학) > BioMedical Science Institute (의생명과학부) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Yonsei Biomedical Research Center (연세의생명연구원) > 1. Journal Papers
Yonsei Authors
Kim, Hye Ryun(김혜련) ORCID logo https://orcid.org/0000-0002-1842-9070
Park, Hye Ji(박혜지)
Lim, Sun Min(임선민)
Cho, Byoung Chul(조병철) ORCID logo https://orcid.org/0000-0002-5562-270X
Han, Joo Yeun(한주연)
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