earticle

영어

The epidermal growth factor receptor (EGFR) overexpressed in many epithelial tumors is an attractive target for tumor therapy since numerous blocking agents of EGFR signaling have proven their anti-tumor activity. A novel monoclonal antibody (mAb), A13, was generated from
mice immunized with human cervical carcinoma A431 cells. In addition to binding to soluble EGFR with affinity of ~5.8 nM, the A13 mAb specifically bound to a variety of tumor cells expressing EGFR. A13 mAb efficiently inhibited both EGF & transforming growth factor (TGF)-α
dependant EGFR tyrosine phosphorylation in cervical and breast tumor cells and also in vitro colony formation of EGFR-overexpressing lung tumors. Competition and sandwich ELISAs, competitive surface plasmon resonance, and domain-level epitope mapping analyses demonstrated that mAb A13 competitively bound to the domain III (amino acids 302-503) of EGFR with EGF, but recognized distinct epitopes from those of cetuximab (Erbitux®). Human monoclonal antibodies selected from a human antibody library based on the A13 mAb reflected the biochemical properties of A13 mAb and one of them, ER2, is being developed for cancer therapeutics.