Tumor-associated truncated O-glycopeptide epitope (TACA)

Tumor-associated truncated O-glycopeptide epitopes represent a class of neoantigens resulting from aberrant glycosylation in malignant cells. In healthy tissues, O-glycans are typically extended into complex branched structures; however, in many adenocarcinomas, the glycosylation process is disrupted, leading to the expression of shortened chains such as the Tn (N-acetylgalactosamine) and Sialyl-Tn (STn) antigens (Pinho & Reis, 2015). These truncated glycans, when attached to specific peptide backbones like those of Mucin 1 (MUC1), form unique glycopeptide epitopes that are highly tumor-specific (Beatson et al., 2016). These epitopes play significant roles in promoting tumor invasion, metastasis, and immune evasion by altering cell-cell interactions and signaling pathways. Therapeutically, these structures are targeted by monoclonal antibodies, glycopeptide-based vaccines, and chimeric antigen receptor (CAR) T-cells to selectively eliminate cancer cells while sparing normal tissue (Posey et al., 2016). Clinical development in this area focuses on overcoming the challenges of glycan heterogeneity and enhancing the durability of the immune response against these specific carbohydrate-peptide motifs.

Other names

Tn antigenSialyl-Tn antigenSTn antigenThomsen-Friedenreich antigenT antigenMUC1-TnMUC1-STnTumor-associated carbohydrate antigenAberrant O-glycan neoepitope

Antibody-dependent cellular cytotoxicity (ADCC), T-cell mediated cytotoxicity, Complement-dependent cytotoxicity (CDC), Immune activation via vaccination