Definition

An antibody-drug conjugate (ADC) consisting of a human monoclonal antibody against neutral amino acid transporter B(0) (ASCT2; SLC1A5) that is site-specifically conjugated, via a protease-cleavable linker, to the cytotoxic, DNA minor-groove crosslinking agent pyrrolobenzodiazepine (PBD) dimer, with potential antineoplastic activity. Upon administration of anti-ASCT2 ADC MEDI7247, the antibody moiety targets and binds to ASCT2 expressed on cancer cells. Upon antibody/antigen binding, internalization and linker cleavage, the cytotoxic PBD moiety is released. In turn, the imine groups of the PBD moiety bind to the N2 positions of guanines on opposite strands of DNA. This induces DNA strand breaks, inhibits DNA replication, leads to G2/M cell cycle arrest, induces cell death, and inhibits the proliferation of ASCT2-overexpressing tumor cells. ASCT2, a neutral amino acid transporter that mediates the uptake of glutamine, is overexpressed in a variety of cancer cell types.