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

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4 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)57-64
Number of pages8
JournalLung Cancer
Volume95
DOIs
Publication statusPublished - 2016 May 1

All Science Journal Classification (ASJC) codes

  • Oncology
  • Pulmonary and Respiratory Medicine
  • Cancer Research

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    Kang, H. N., Kim, S. H., Yun, M. R., Kim, H. R., Lim, S. M., Kim, M. S., Hong, K. W., Kim, S. M., Kim, H., Pyo, K. H., Park, H. J., Han, J. Y., Youn, H. A., Chang, K. H., & Cho, B. C. (2016). ER2, a novel human anti-EGFR monoclonal antibody inhibit tumor activity in non-small cell lung cancer models. Lung Cancer, 95, 57-64. https://doi.org/10.1016/j.lungcan.2016.02.013