A1mcMMAF

A1mcMMAF (also known as PF-06263507 or A1-mafodotin) is an antibody-drug conjugate (ADC) targeting 5T4 (trophoblast glycoprotein), an oncofetal antigen expressed on tumor-initiating cells and various solid tumors. Developed by Pfizer in collaboration with Oxford BioMedica, the ADC consists of a humanized anti-5T4 IgG1 monoclonal antibody (A1) conjugated to the microtubule-disrupting agent monomethyl auristatin F (MMAF) via a non-cleavable maleimidocaproyl (mc) linker. Upon binding to 5T4 on the cell surface, the ADC is rapidly internalized and trafficked to lysosomes, where proteolytic degradation releases the active Cys-capped mc-MMAF payload, leading to cell cycle arrest and apoptosis. A Phase I clinical trial in patients with advanced solid tumors was initiated, but development was discontinued in 2015 due to a lack of objective clinical responses and dose-limiting ocular toxicities.

Other names

A1-mafodotinA-1-mafodotinA 1-mafodotinanti-5T4 antibody-drug conjugateanti5T4 antibody-drug conjugateanti 5T4 antibody-drug conjugate