anti-Claudin 18.2 antibody-drug conjugate SOT102

An antibody-drug conjugate (ADC) composed of an immunoglobulin G1 (IgG1) monoclonal antibody directed against the tumor-associated antigen (TAA) claudin 18.2 (CLDN18.2; A2 isoform of claudin-18) that is site-specifically conjugated, via a non-cleavable amide/peptide linker, to a derivative of the cytotoxic anthracycline PNU-159682, with potential antineoplastic activity. Upon administration of anti-CLDN18.2 ADC SOT102, the antibody moiety specifically targets and binds to CLDN18.2 expressed on tumor cells. Upon internalization, the anthracycline-based toxin intercalates into DNA and interacts with topoisomerase II. This leads to an inhibition of DNA replication and repair, and prevents RNA and protein synthesis. This kills the CLDN18.2-expressing tumor cells. 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.