T-cell receptor specific for MUC4 peptide–MHC complex (TCR-MUC4/MHC)

T-cell receptors (TCRs) specific for MUC4 peptide–MHC complexes are engineered or naturally occurring immune receptors designed to recognize Mucin-4 (MUC4) antigens presented by Major Histocompatibility Complex (MHC) molecules. MUC4 is a high-molecular-weight transmembrane glycoprotein that is significantly overexpressed in various malignancies, most notably pancreatic ductal adenocarcinoma (PDAC), while remaining largely absent in the normal pancreas (Gautam et al., 2020, Semin Immunol). These TCRs enable T cells to specifically identify and eliminate MUC4-positive tumor cells by binding to specific MUC4-derived peptides, such as those restricted by HLA-A*02:01 (NIH, 2021). This target is a focal point for adoptive T-cell therapies, including TCR-engineered T (TCR-T) cells, which aim to overcome the immunosuppressive tumor microenvironment and provide a precise treatment for solid tumors. However, therapeutic development must address potential on-target off-tumor toxicities, as MUC4 is expressed at lower levels in some normal epithelial tissues like salivary glands and the reproductive tract, and tumor-mediated mechanisms that can induce T-cell exhaustion or apoptosis (NIH, 2020; BioRxiv, 2026).

Other names

MUC4-specific T-cell receptorMUC4-targeted TCRMUC4-pMHC-specific TCRMucin-4-specific T-cell receptor

Recognition of MUC4-derived peptides presented by MHC (HLA) molecules on the surface of tumor cells, leading to T-cell activation and targeted lysis of the cancer cells.