Mucin 17–Cluster of differentiation 3 complex (MUC17–CD3)

Mucin 17 (MUC17) is a high-molecular-weight, membrane-bound glycoprotein primarily expressed in the apical membrane of the intestinal epithelium, where it contributes to the protective mucosal barrier [1]. In the context of oncology, MUC17 is frequently overexpressed in gastric, gastroesophageal junction, and pancreatic cancers, while showing limited expression in most normal tissues outside the gastrointestinal tract [2]. The MUC17–CD3 cell–cell interface is a therapeutic target created by bispecific T-cell engagers (BiTEs), which are designed to physically link MUC17-positive tumor cells to CD3-positive T-cells [3]. This interaction facilitates the formation of a cytolytic synapse, leading to the activation of T-cells and the subsequent release of perforins and granzymes that induce apoptosis in the target cancer cell [4]. By bypassing the requirement for major histocompatibility complex (MHC) class I presentation, this target allows for a potent and specific immune attack against tumors that might otherwise evade detection [5]. Clinical development of drugs targeting this interface, such as AMG 199, focuses on treating advanced gastrointestinal malignancies, though management of cytokine release syndrome (CRS) and potential on-target off-tumor effects in the normal intestinal lining are critical safety considerations [6].

Other names

MUC17 x CD3MUC17-CD3 BiTE targetMUC17-CD3 T-cell engager targetMucin 17/CD3 epsilon complex

Bispecific T-cell engagement leading to redirected T-cell cytotoxicity against MUC17-expressing tumor cells.