Epithelial cell adhesion molecule and CD3 T-cell coreceptor (EpCAM/CD3)

The EpCAM/CD3 target complex represents a bispecific therapeutic approach designed to bridge the gap between epithelial tumor cells and the immune system (UniProt P16422, P07766). Epithelial cell adhesion molecule (EpCAM) is a transmembrane glycoprotein highly overexpressed in various carcinomas, including colorectal, gastric, and lung cancers, where it plays roles in cell signaling, migration, and proliferation (PubMed: 20490308). CD3 is a multi-subunit protein complex found on the surface of T cells that is essential for T-cell receptor signaling and activation. By simultaneously binding to EpCAM on cancer cells and CD3 on T cells, bispecific antibodies or T-cell engagers (BiTEs) bypass the need for traditional major histocompatibility complex (MHC) recognition (PubMed: 19550605). This interaction triggers the formation of an immunological synapse, leading to the release of perforins and granzymes by T cells, which results in the targeted destruction of the tumor cell. This strategy has been clinically utilized in the treatment of malignant ascites and is being explored for various solid tumors, though challenges remain regarding on-target off-tumor toxicity in normal epithelial tissues (PubMed: 20124321).

Other names

Ep-CAM/CD3CD326/CD3TACSTD1/CD3Epithelial glycoprotein 2/CD3GA733-2/CD3TROP1/CD3

Bispecific T-cell engagement (BiTE) or trifunctional antibody binding that brings T cells into close proximity with EpCAM-expressing tumor cells, leading to T-cell activation and directed lysis of the cancer cells.