Discovery of amivantamab (JNJ-61186372), a bispecific antibody targeting EGFR and MET.

ABSTRACT: A bispecific antibody (BsAb) targeting the epidermal growth factor receptor (EGFR) and mesenchymal-epithelial transition factor (MET) pathways represents a novel approach to overcome resistance to targeted therapies in patients with non-small cell lung cancer. In this study, we sequentially screened a panel of BsAbs in a combinatorial approach to select the optimal bispecific molecule. The BsAbs were derived from different EGFR and MET parental monoclonal antibodies. Initially, molecules were screened for EGFR and MET binding on tumor cell lines and lack of agonistic activity toward MET. Hits were identified and further screened based on their potential to induce untoward cell proliferation and cross-phosphorylation of EGFR by MET via receptor colocalization in the absence of ligand. After

SUBMITTER: Neijssen J 

PROVIDER: S-EPMC8113745 | biostudies-literature | 2021 Jan-Jun

REPOSITORIES: biostudies-literature