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Lung Cancer. 2016 May;95:57-64. doi: 10.1016/j.lungcan.2016.02.013. Epub 2016 Feb 27.

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

Author information

1
JEUK Institute for Cancer Research, JEUK Co., Ltd., Gumi-City, Kyungbuk, Republic of Korea.
2
University-Industry Cooperation Foundation, and Department of Systems Immunology, College of Biomedical Science, Kangwon National University, Chuncheon, Kangwon-Do, Republic of Korea.
3
Division of Medical Oncology, Yonsei Cancer Center, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea.
4
Antibody Engineering 1 Team, Mogam Biotechnology Research Institute Yongin, Republic of Korea.
5
Cell Engineering team, Green Cross Research Center, Green Cross Corp., Yongin, Republic of Korea.
6
Antibody Engineering 1 Team, Mogam Biotechnology Research Institute Yongin, Republic of Korea; Department of Biochemistry, Yonsei University, Seoul, Republic of Korea. Electronic address: jkhdw@mogam.re.kr.
7
Brain Korea 21 Project for Medical Sciences, Yonsei University College of Medicine, Seoul, Republic of Korea; Division of Medical Oncology, Yonsei Cancer Center, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea. Electronic address: cbc1971@yuhs.ac.

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.

KEYWORDS:

Cetuximab; ER2; Epidermal growth factor receptor; Monoclonal antibody; Non-small cell lung cancer

PMID:
27040853
DOI:
10.1016/j.lungcan.2016.02.013
[Indexed for MEDLINE]

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