Cancer-associated glycopeptide epitope

Cancer-associated glycopeptide epitopes are neoantigens characterized by the presence of truncated O-glycans, such as the Tn (GalNAc), Sialyl-Tn (STn), and Thomsen-Friedenreich (TF) antigens, on the peptide backbone of cell-surface glycoproteins [PubMed, 2016]. In healthy cells, O-glycans are typically extended into complex, branched structures; however, in many carcinomas, the dysregulation of glycosyltransferases—often due to mutations or epigenetic silencing of the COSMC chaperone—leads to the premature termination of glycan synthesis [PNAS, 2021]. This truncation exposes glyco-neoepitopes that consist of both the carbohydrate moiety and the underlying peptide sequence, which are largely absent in normal tissues [Nature, 2020]. These epitopes, particularly when displayed on proteins like MUC1, CD44, and TAG-72, are involved in cancer progression by facilitating cell adhesion, invasion, and immune evasion [Frontiers in Oncology, 2024]. Therapeutic interventions targeting these epitopes include monoclonal antibodies like Gatipotuzumab, vaccines such as Theratope, and CAR-T cell therapies, which leverage the high tumor specificity of these structures to target malignant cells while sparing healthy tissue [Cell Reports Medicine, 2025].

Other names

Cancer-associated cell-surface glycopeptide epitopes bearing truncated O-glycans on membrane glycoproteins of carcinoma cellsTumor-associated glycopeptide epitopeGlyco-neoepitopeTruncated O-glycan epitopeTn-glycopeptideSTn-glycopeptideCancer-associated O-glycan epitopeTumor-associated carbohydrate antigen (TACA) epitope

Drugs targeting these epitopes primarily function by inducing immune-mediated destruction of cancer cells. This includes antibody-dependent cellular cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC) for monoclonal antibodies, the induction of tumor-specific T-cell and B-cell responses for vaccines, and direct T-cell mediated killing for chimeric antigen receptor (CAR) T-cell therapies [NIH, 2012; Cell Reports Medicine, 2025].