Claudin 18.2 (CLDN18.2)

Class

CLDN18.2-targeted antibody-drug conjugate

Pathway

Antibody-drug conjugate delivering a cytotoxic payload to CLDN18.2-expressing tumor cells; licensed by Astellas from Evopoint

Claudin 18.2 (CLDN18.2) is a member of the claudin family of four-transmembrane proteins that form tight junctions, the seals between adjacent epithelial cells that maintain barrier integrity. In healthy tissue, expression of this particular claudin isoform is largely confined to differentiated cells lining the stomach, where it sits within tight junction complexes and is largely inaccessible to circulating molecules. During malignant transformation, gastric and gastroesophageal junction cancers, and a subset of pancreatic cancers, frequently retain or upregulate CLDN18.2 while losing normal epithelial architecture, which exposes the protein on the tumor cell surface. This combination of tumor-associated exposure and restricted normal-tissue distribution makes it an attractive antigen for targeted therapy. An antibody-drug conjugate (ADC) exploits this by pairing an antibody that recognizes CLDN18.2 with a potent cytotoxic payload, using the antibody to concentrate cell-killing chemistry specifically at tumor sites rather than distributing it systemically. This strategy is relevant across gastrointestinal malignancies where CLDN18.2 expression is common and where conventional chemotherapy options remain limited in durability, offering a way to combine tumor selectivity with cytotoxic potency.