Definition

An antibody-drug conjugate (ADC) composed of a humanized monoclonal antibody directed against the tumor-associated antigen (TAA) Claudin 18.2 (CLDN18.2; A2 isoform of claudin-18) conjugated to the microtubule-disrupting cytotoxic agent monomethyl auristatin E (MMAE), with potential antineoplastic activity. Upon administration, anti-CLDN18.2 ADC JS107 specifically targets and binds to CLDN18.2 expressed on tumor cells. Upon internalization and the release of MMAE, MMAE targets and binds to tubulin, and inhibits microtubule polymerization. This results in G2/M phase cell cycle arrest and apoptosis in CLDN18.2-expressing tumor cells. In addition, JS107 kills tumor cells via antibody-dependent cellular cytotoxicity (ADCC) and complement dependent cytotoxicity (CDC). CLDN18.2, a tight junction protein and stomach-specific isoform of claudin-18, is expressed on a variety of tumor cells. Its expression in healthy tissues is strictly confined to short-lived differentiated epithelial cells of the gastric mucosa.