T-cell receptors specific for HLA-MUC1-SP complexes (MUC1-SP TCR)

T-cell receptors (TCRs) specific for HLA-MUC1-SP complexes are a class of engineered or naturally occurring immune receptors designed to recognize a specific peptide derived from the signal peptide (SP) of Mucin 1 (MUC1) when presented by Human Leukocyte Antigen (HLA) molecules, most commonly HLA-A*02:01 (1.1.1, 2.3.2). MUC1 is a transmembrane glycoprotein that is significantly overexpressed and aberrantly glycosylated in various malignancies, including multiple myeloma and solid tumors, where it contributes to tumor cell adhesion and signaling (1.2.3, 4.3.3). While many MUC1-targeted therapies focus on the extracellular tandem repeat domain, the signal peptide is processed and presented via the classical MHC class I pathway, providing a unique target for T-cell-based immunotherapies (1.3.4, 2.3.3). These TCRs are primarily utilized in the development of TCR-engineered T cell (TCR-T) therapies, which aim to redirect the patient's immune system to specifically identify and eliminate MUC1-positive malignant cells (1.1.1, 4.4.4). Therapeutic strategies targeting this complex include the peptide vaccine ImMucin (VXL100), which induces endogenous T-cell responses against the MUC1-SP complex, and TCR-like antibodies such as SPmAb-2.1 that recognize the same peptide-MHC configuration (1.2.1, 4.2.3). Safety considerations for these therapies include potential off-target recognition of similar self-peptides and systemic inflammatory responses like cytokine release syndrome (1.2.4, 4.4.4).

Other names

MUC1-SP specific T-cell receptorsHLA-A*02:01-restricted MUC1 signal peptide TCRsT-cell receptors specific for HLA-A*02:01-restricted MUC1 signal peptide complexes

These T-cell receptors (TCRs) specifically recognize the Mucin 1 signal peptide (MUC1-SP) presented by HLA-A*02:01 on the surface of tumor cells, triggering T-cell activation and the subsequent cytotoxic lysis of the cancer cells.