Claudin 18 isoform 2 (CLDN18.2) (CLDN18.2)

Claudin 18 isoform 2 (CLDN18.2) is a highly specific cell-surface protein belonging to the claudin family, which are critical components of tight junction complexes that maintain cell polarity and regulate paracellular transport [3]. In healthy individuals, CLDN18.2 expression is strictly confined to the differentiated epithelial cells of the gastric mucosa, where it is typically buried within tight junctions and inaccessible to the immune system [4]. However, in several types of adenocarcinoma—most notably gastric, pancreatic, and esophageal cancers—CLDN18.2 is frequently overexpressed and becomes exposed on the cell surface as a result of the loss of cellular adhesion and polarity [5]. This unique expression profile makes it an ideal tumor-associated antigen for targeted therapies. VCB-1204 is an investigational CAR-T cell therapy developed by VcanBio that specifically targets CLDN18.2-positive tumor cells [1]. By redirecting the immune system to recognize this specific isoform, VCB-1204 aims to provide a potent and selective treatment option for patients with advanced gastrointestinal malignancies [7].

Other names

Claudin-18.2CLDN18 isoform 2Claudin-18 splice variant 2

VCB-1204 is a chimeric antigen receptor (CAR) T-cell therapy where patient-derived T-cells are genetically engineered to express a CAR specific for the Claudin 18.2 (CLDN18.2) antigen. Upon infusion, these CAR-T cells recognize and bind to the extracellular domain of CLDN18.2 on the surface of tumor cells. This binding event triggers the activation of the T-cell's signaling domains (typically CD3-zeta and co-stimulatory domains like 4-1BB or CD28), leading to the release of cytotoxic molecules such as perforin and granzymes, as well as the production of pro-inflammatory cytokines, which collectively mediate the lysis of the target cancer cells [1, 2, 6].