T cell receptor recognizing MHC–MUC1 peptide complexes (TCR-MUC1/MHC)

The T cell receptor (TCR) recognizing MHC–MUC1 peptide complexes is a specialized immune receptor designed to target Mucin 1 (MUC1), a transmembrane glycoprotein that is overexpressed and aberrantly glycosylated in many epithelial cancers, including breast, pancreatic, and lung carcinomas (Nath & Mukherjee, 2014). Unlike antibodies that recognize the native protein surface, these TCRs recognize specific MUC1-derived peptides presented by Major Histocompatibility Complex (MHC) molecules, such as HLA-A*02:01, on the cell surface (Madsen et al., 2013). This recognition mechanism allows the immune system to target epitopes that may be hidden or intracellularly processed, providing a highly specific pathway for tumor destruction. In clinical applications, T cells are often genetically engineered to express these MUC1-specific TCRs (TCR-T therapy) to enhance the patient's anti-tumor immune response (Zhou et al., 2019). While promising, the use of these receptors faces challenges such as "on-target, off-tumor" toxicity, as low levels of MUC1 are present on normal epithelial cells, and the requirement for patients to possess specific HLA alleles for the therapy to be effective (NCT02588612).

Other names

MUC1-specific T-cell receptorMUC1-targeted TCRMHC-restricted MUC1-specific TCRMUC1-specific TCR

Engineered T cells expressing the MUC1-specific TCR bind to MUC1 peptide-MHC complexes on the surface of tumor cells, leading to T cell activation, secretion of cytotoxic granules (perforin and granzymes), and tumor cell lysis.