title: ER2, a novel human anti-EGFR monoclonal antibody inhibit tumor activity in non-small cell lung cancer models.
abstract: OBJECTIVE
  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.
  
  
  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.
authors.affiliation: JEUK Institute for Cancer Research, JEUK Co., Ltd., Gumi-City, Kyungbuk, Republic of Korea.
authors.forename: Han Na
authors.initials: HN
authors.lastname: Kang
authors.affiliation: University-Industry Cooperation Foundation, and Department of Systems Immunology, College of Biomedical Science, Kangwon National University, Chuncheon, Kangwon-Do, Republic of Korea.
authors.forename: Se-Ho
authors.initials: SH
authors.lastname: Kim
authors.affiliation: JEUK Institute for Cancer Research, JEUK Co., Ltd., Gumi-City, Kyungbuk, Republic of Korea.
authors.forename: Mi Ran
authors.initials: MR
authors.lastname: Yun
authors.affiliation: Division of Medical Oncology, Yonsei Cancer Center, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea.
authors.forename: Hye Ryun
authors.initials: HR
authors.lastname: Kim
authors.affiliation: Division of Medical Oncology, Yonsei Cancer Center, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea.
authors.forename: Sun Min
authors.initials: SM
authors.lastname: Lim
authors.affiliation: Antibody Engineering 1 Team, Mogam Biotechnology Research Institute Yongin, Republic of Korea.
authors.forename: Min-Soo
authors.initials: MS
authors.lastname: Kim
authors.affiliation: Cell Engineering team, Green Cross Research Center, Green Cross Corp., Yongin, Republic of Korea.
authors.forename: Kwang-Won
authors.initials: KW
authors.lastname: Hong
authors.affiliation: JEUK Institute for Cancer Research, JEUK Co., Ltd., Gumi-City, Kyungbuk, Republic of Korea.
authors.forename: Sung-Moo
authors.initials: SM
authors.lastname: Kim
authors.affiliation: JEUK Institute for Cancer Research, JEUK Co., Ltd., Gumi-City, Kyungbuk, Republic of Korea.
authors.forename: Hwan
authors.initials: H
authors.lastname: Kim
authors.affiliation: JEUK Institute for Cancer Research, JEUK Co., Ltd., Gumi-City, Kyungbuk, Republic of Korea.
authors.forename: Kyoung-Ho
authors.initials: KH
authors.lastname: Pyo
authors.affiliation: Division of Medical Oncology, Yonsei Cancer Center, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea.
authors.forename: Hye Ji
authors.initials: HJ
authors.lastname: Park
authors.affiliation: Division of Medical Oncology, Yonsei Cancer Center, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea.
authors.forename: Joo Yeun
authors.initials: JY
authors.lastname: Han
authors.affiliation: Division of Medical Oncology, Yonsei Cancer Center, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea.
authors.forename: Hyun A
authors.initials: HA
authors.lastname: Youn
authors.affiliation: 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.
authors.forename: Ki-Hwan
authors.initials: KH
authors.lastname: Chang
authors.affiliation: 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.
authors.forename: Byoung Chul
authors.initials: BC
authors.lastname: Cho
mesh_terms: D000818:Animals; D061067:Antibodies, Monoclonal, Humanized / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology*; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000494:pharmacology; D004195:Disease Models, Animal; D004357:Drug Synergism; D066246:ErbB Receptors / Q000037:antagonists & inhibitors* / Q000378:metabolism; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology*; D051379:Mice; D015398:Signal Transduction / Q000187:drug effects; D023041:Xenograft Model Antitumor Assays
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D066246:ErbB Receptors; D002945:Cisplatin
keywords: Cetuximab; ER2; Epidermal growth factor receptor; Monoclonal antibody; Non-small cell lung cancer