Mucin 1-specific T-cell receptor (MUC1-specific TCR)

Mucin 1-specific T-cell receptors (MUC1-specific TCRs) are specialized immune receptors engineered into CD4+ and CD8+ T lymphocytes to facilitate the targeted destruction of MUC1-expressing malignant cells. MUC1 is a heavily O-glycosylated transmembrane protein that is overexpressed and loses its apical polarization in over 90% of adenocarcinomas, including breast, pancreatic, and lung cancers, making it a premier target for immunotherapy (Nath & Mukherjee, 2014). These TCRs are designed to recognize MUC1-derived peptides, such as those from the variable number tandem repeat (VNTR) or signal sequence regions, presented by specific Human Leukocyte Antigen (HLA) alleles, most commonly HLA-A*02:01 (Schuster et al., 2021). By utilizing the endogenous T-cell signaling machinery, MUC1-specific TCR-T cells can mount a potent cytotoxic response against tumor cells while potentially offering better penetration into solid tumors compared to traditional antibodies. However, the therapeutic window is narrowed by the expression of MUC1 on the surface of normal secretory epithelial cells, necessitating careful selection of TCR affinity to minimize on-target off-tumor toxicities (Casucci et al., 2013). Current clinical strategies involve the use of these TCRs in adoptive cell transfer (ACT) to treat advanced solid tumors and hematological malignancies like multiple myeloma.

Other names

MUC1-targeted TCRMUC1-specific T-cell receptor complexMucin 1-specific TCR

Recognition of MUC1-derived peptides presented by Major Histocompatibility Complex (MHC) molecules on the surface of tumor cells, leading to T-cell activation, cytokine production, and targeted lysis of MUC1-expressing cells (Schuster et al., 2021; Nath & Mukherjee, 2014).