monospecific epidermal growth factor receptor antibody-drug conjugate

A monospecific epidermal growth factor receptor (EGFR) antibody-drug conjugate (ADC) is a targeted cancer therapeutic designed to deliver a potent cytotoxic agent directly to cells expressing EGFR. This modality comprises a monoclonal antibody specific for the extracellular domain of EGFR, linked via a stable chemical spacer to a payload such as a microtubule inhibitor (e.g., monomethyl auristatin F) or a DNA-damaging agent. EGFR is a well-validated oncogenic driver frequently overexpressed or mutated in solid tumors, including non-small cell lung cancer (NSCLC), colorectal cancer, and glioblastoma. Upon binding to the receptor, the ADC is internalized through receptor-mediated endocytosis and trafficked to the lysosome, where the payload is released to exert its cytotoxic effect. This approach aims to improve the therapeutic window of EGFR-targeted therapy by minimizing the systemic toxicity associated with conventional chemotherapy and the skin toxicities often seen with EGFR tyrosine kinase inhibitors or naked antibodies. Several monospecific EGFR ADCs, such as depatuxizumab mafodotin (ABT-414) and MRG003, have been evaluated in clinical trials.

Other names

EGFR ADCanti-EGFR ADCEGFR-targeted antibody-drug conjugate