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Depatuxizumab mafodotin is an antibody-drug conjugate (ADC) developed for the treatment of cancer, particularly glioblastoma and other solid tumors. It consists of a humanized IgG1 monoclonal antibody (depatuxizumab) targeting the epidermal growth factor receptor (EGFR), including tumor-specific EGFR epitopes and mutant forms such as EGFRvIII, conjugated via a stable maleimidocaproyl linker to the cytotoxic agent monomethyl auristatin F (MMAF), a tubulin inhibitor. Upon binding to EGFR-expressing tumor cells, the ADC is internalized and releases MMAF intracellularly, leading to inhibition of tubulin polymerization, mitotic arrest, apoptosis induction, and subsequent cell death. The drug was granted orphan drug status for glioblastoma but its development was discontinued after late-stage clinical trial failures[1][3][5][6].
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