anti-CLDN6/9 antibody-drug conjugate SC-004

An antibody-drug conjugate (ADC) composed of a proprietary monoclonal antibody directed against claudin-6 (CLDN6; CLDN-6) and claudin-9 (CLDN9; CLDN-9) linked to a cytotoxic pyrrolobenzodiazepine (PBD) dimer, with potential antineoplastic activity. Upon intravenous administration, the monoclonal antibody moiety of anti-CLDN6/9 ADC SC-004 targets and binds to CLDN6/9 expressed on tumor cells, and the PBD moiety 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 CLDN6/9-overexpressing tumor cells. CLDN6, a transmembrane tight-junction protein and embryonic antigen, is overexpressed on a variety of tumor cells but is not expressed on normal, healthy adult cells. CLDN6 and CLDN9 differ at only 3 out of 76 residues in their extracellular loops, and CLDN9 is highly expressed in some normal tissues in addition to some tumors.