HLA class I-MUC1 signal peptide complex (HLA-I/MUC1-SP)

The HLA class I-MUC1 signal peptide complex is a tumor-associated antigen (TAA) consisting of a specific peptide derived from the signal sequence of the Mucin 1 (MUC1) protein, presented by Human Leukocyte Antigen (HLA) class I molecules, most commonly HLA-A*02:01 (PMID: 11544313). MUC1 is a transmembrane glycoprotein that is significantly overexpressed and aberrantly glycosylated in a wide range of epithelial cancers, including breast, ovarian, and pancreatic malignancies (PMID: 21602448). While the full-length MUC1 protein is a target for traditional monoclonal antibodies, the signal peptide is processed intracellularly and presented on the cell surface, providing a unique target for T-cell receptor (TCR)-based immunotherapies (PMID: 15585875). These therapeutic approaches, such as TCR-engineered T cells (TCR-T) and TCR-like antibodies, are designed to recognize the peptide-HLA complex with high specificity, leading to the activation of cytotoxic T cells and the subsequent destruction of tumor cells. This target is particularly attractive because the signal peptide is highly conserved and its presentation is relatively restricted to malignant cells, potentially reducing off-target toxicity compared to therapies targeting the protein's extracellular domain. However, the clinical application of these therapies is limited by HLA restriction, requiring patients to possess specific HLA alleles for the treatment to be effective.

Other names

MUC1 signal peptide-HLA-A*02:01 complexMUC1-SP/HLA complexMUC1 signal peptide-MHC class I complexHLA-A2/MUC1-SP

T-cell redirection and mediated cytotoxicity through specific TCR-mediated recognition of the peptide-HLA complex.