Preclinical activity for TPX-4589 (LM-302), an antibody-drug conjugate targeting tight junction protein CLDN18.2 in solid tumors

Background: Claudin 18 isoform 2 (CLDN18.2) is a tight junction protein involved in the regulation of epithelial cell permeability, barrier function, and polarity. In healthy tissue, CLDN18.2 is selectively expressed in tight junctions of gastric epithelial tissue and hence largely inaccessible to intravenous antibodies. On malignant transformation, CLDN18.2 is exposed on the cancer cell surface and expressed in many solid tumors, including gastric cancer (GC) and pancreatic cancer (PC). CLDN18.2 expression is associated with tumor pathogenesis, proliferation, and metastasis, making it a promising target for cancer therapies.