anti-DLL3 antibody-drug conjugate SC-002

An antibody-drug conjugate (ADC) composed of a monoclonal antibody directed against the tumor-associated antigen (TAA) delta-like protein 3 (DLL3), site-specifically conjugated to the cytotoxic pyrrolobenzodiazepine (PBD) dimer SC-DR002 via a plasma-stable valine-alanine dipeptide linker, with potential antineoplastic activity. Upon intravenous administration, the monoclonal antibody moiety of anti-DLL3 ADC SC-002 targets and binds to DLL3 expressed on tumor cells. Upon binding and internalization, the dipeptide linker is cleaved upon cathepsin-mediated proteolysis and SC-DR002 is released. Then 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 DLL3-overexpressing tumor cells. DLL3, a membrane protein that binds to Notch receptors and regulates Notch-mediated signaling and gene transcription, is overexpressed by certain cancers but is rarely expressed by normal, healthy cells.