Tumor-associated Mucin 1 peptide-MHC complex (TA-MUC1-pMHC)

Mucin 1 (MUC1) is a high-molecular-weight transmembrane glycoprotein that is normally expressed on the apical surface of epithelial cells, where it serves a protective and lubricating role (UniProt P15941). In many cancers, MUC1 is overexpressed, loses its apical polarity, and undergoes aberrant glycosylation, which facilitates the processing and presentation of unique MUC1-derived peptide epitopes on Major Histocompatibility Complex (MHC) molecules (PMID: 24713730). These tumor-associated MUC1 peptide-MHC complexes (TA-MUC1-pMHC) are recognized as foreign by the immune system, making them prime targets for immunotherapeutic interventions such as T-cell receptor (TCR)-engineered T cells and TCR-like antibodies (PMID: 30554175). Unlike traditional MUC1-targeting antibodies that bind to the protein's extracellular domain, therapies targeting the pMHC complex can specifically eliminate cells presenting internal MUC1 fragments, potentially increasing specificity for malignant cells (PMID: 15150570). This target is particularly relevant in adenocarcinomas of the breast, lung, and pancreas, where MUC1 presentation is a hallmark of the disease state.

Other names

MUC1-HLA complexMUC1-MHC complexMucin 1 peptide-HLA-A2 complexTA-MUC1 peptide epitopeMUC1-derived peptide-MHC

Targeting of MUC1-derived peptides presented by MHC molecules to trigger T-cell mediated lysis of tumor cells