129PD - ER2, a novel human anti-EGFR monoclonal antibody inhibit tumor activity in non-small cell lung cancer models

Date 20 December 2015
Event ESMO Asia 2015 Congress
Session Developmental therapeutics
Topics Drug Development
Basic Science
Lung and other Thoracic Tumours
Translational Research
Presenter Byoung Chul Cho
Citation Annals of Oncology (2015) 26 (suppl_9): 37-39. 10.1093/annonc/mdv521
Authors B.C. Cho
  • Medical Oncology, Yonsei Cancer Center, 120-752 - Seoul/KR

Abstract

Aim/Background

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. 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) were 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 and HCC827 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 and HCC827 cells. Moreover, ER2 alone and in combination with cisplatin showed a significant anti-tumor efficacy in xenograft mouse models.

Conclusions

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.

Clinical trial identification

Disclosure

All authors have declared no conflicts of interest.