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

作者：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^*

来源：Lung Cancer, 2016, 95: 57-64.

DOI：10.1016/j.lungcan.2016.02.013

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

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 PC9GR) 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 Ala and Erkl/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.

• 出版日期2016-5