anti-TF antibody-drug conjugate MRG004A

An antibody-drug conjugate (ADC) comprised of a monoclonal antibody against human tissue factor (TF) conjugated, via a protease-cleavable BCN-valyl-citrulline linker, with monomethyl auristatin E (MMAE), an auristatin derivative and potent microtubule disrupting agent, with potential antiangiogenic, anticoagulant and antineoplastic activities. Upon administration of anti-TF ADC MRG004A, the monoclonal antibody moiety binds to cell surface TF and is internalized. After internalization of the agent, the MMAE moiety is released by proteolytic cleavage. It then binds to tubulin and inhibits its polymerization, which results in G2/M phase arrest and apoptosis. TF, a transmembrane protein and initiator of the coagulation cascade, is overexpressed in many tumor cells and tumor-resident endothelial cells. Expression of TF is correlated with metastasis, angiogenesis, tumor cell growth and tumor-associated thrombosis.