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Antitumor Activity of ME22S, a Novel EGFR/Met Bispecific Therapeutic Antibody in Human Laryngeal Carcinoma
Dept. of Otolaryngology1, Center for Cell Death Regulating Biodrug, School of Medicine2, Dept. of Molecular Science and Technology3, Ajou Univ., Bio Therapeutics Lab, Samsung Advanced Institute of Technology (SAIT)/ Samsung Electronics Co. Ltd4
Bok-Soon LEE, Bok-Soon LEE12, Haeng-Jun KIM123, Jae-Woong HWANG4, Kwang Ho CHEONG4, Kyung-Ah KIM4, Hyun-Yong CHA12, Chul-Ho KIM123
¸ñÀû: Expression of Met, a gene for the hepatocyte growth factor (HGF) receptor, is known to be associated with tumor development in several human carcinomas. It is now reported that the high expression of EGFR and Met mediate the invasive growth of laryngeal carcinoma. In this study, for the first time, we evaluated the therapeutic efficacy of ME22S (a novel EGFR/Met bispecific antibody) alone or with HGF in laryngeal carcinoma cell lines. ¹æ¹ý:The effects of ME22S in laryngeal carcinoma cell lines (SNU899 and HN3) was studied on migration and invasion induced by HGF using wound healing assay and invasion assay, respectively. Soft agar assay and Western blot analysis was examined on the co-treatment of HGF and ME22S. In addition, SNU899 or HN3 cell lines were subcutaneous injected into the athymic nude mice respectively. Mice were randomly assigned to treatment with control and ME22S for 4 weeks, then all mice were sacrificed. °á°ú:EGFR/Met inhibition by ME22S resulted in highly significant inhibition on SNU899 or HN3 cell migration, invasion and proliferation in vitro. In addition, we demonstrated that co-treatment of ME22S and HGF blocked the anchorage-independent growth induced by HGF. After ME22S only or co-treatment with HGF, it was significantly showed the inhibition of phospho-ERK. Interestingly, we found that ME22S treatment for 72 h in HN3 cell lines induced the caspase- dependent apoptotic cell death. In addition, ME22S could inhibit the tumor growth of HN3, but dose not inhibit the tumor growth of SNU899.Therefore, the results support that ME22S inhibited the EGFR and Met activation as well as the downstream, thereby, could have a therapeutic potential in laryngeal carcinoma. °á·Ð:We concluded that the dual inhibition of EGFR and Met was effective in suppressing the invasion and growth of laryngeal carcinoma. This new therapeutic strategy may be a practical approach in the treatment of these patients.


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