anti-claudin 18.2 antibody-drug conjugate BL-M05D1

An antibody-drug conjugate (ADC) composed of a wild-type Fc-containing immunoglobulin (IgG) monoclonal antibody directed against the tumor-associated antigen (TAA) claudin 18.2 (CLDN18.2; A2 isoform of claudin-18) (5103F3) conjugated, via a cathepsin B cleavable linker, to the camptothecin derivative and topoisomerase 1 inhibitor Ed-04, with potential antineoplastic activity. Upon administration of anti-CLDN18.2 ADC BL-M05D1, the anti-CLDN18.2 monoclonal antibody moiety specifically targets and binds to CLDN18.2 expressed on tumor cells. Upon binding, internalization and linker cleavage, Ed-04 is released and inhibits DNA topoisomerase I activity, thereby inhibiting DNA replication and resulting in cell cycle arrest and apoptosis in tumor cells expressing CLDN18.2. In addition, BL-M05D1 may mediate antibody-dependent cellular cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC). CLDN18.2, a tight junction protein and stomach-specific isoform of claudin-18, is overexpressed on a variety of tumor cells. Its expression in healthy tissues is strictly confined to short-lived differentiated epithelial cells of the gastric mucosa.