Claudin 18.2 and CD3 receptor complex (CLDN18.2/CD3)

The Claudin 18.2–CD3 interface is a therapeutic target for bispecific T-cell engagers (TCEs) designed to treat solid tumors, particularly gastric and pancreatic cancers. Claudin 18.2 (CLDN18.2) is a tight junction protein with highly restricted expression in normal tissues, limited primarily to the differentiated epithelial cells of the gastric mucosa, but it is frequently overexpressed in various adenocarcinomas. CD3 is a co-receptor complex on T cells essential for signal transduction and activation. By simultaneously binding to CLDN18.2 on tumor cells and CD3 on T cells, bispecific antibodies facilitate the formation of an artificial immune synapse. This interaction redirects cytotoxic T lymphocytes to recognize and eliminate CLDN18.2-positive tumor cells independently of major histocompatibility complex (MHC) restriction. Clinical development of agents targeting this interface, such as IBI389 and AZD5863, aims to enhance anti-tumor efficacy compared to conventional monoclonal antibodies. However, therapeutic application is associated with risks such as cytokine release syndrome (CRS) and on-target off-tumor toxicities in the stomach.

Other names

CLDN18.2 x CD3Claudin 18.2/CD3CLDN18.2-CD3 bispecific targetClaudin 18.2–CD3 interface

T-cell redirection and engagement; the bispecific antibody binds to Claudin 18.2 on tumor cells and CD3 on T cells to form an immune synapse, triggering T-cell activation and subsequent tumor cell lysis via perforin and granzyme release.