Mucin 1 with Tn antigen (Tn-MUC1) (Tn-MUC1)

Mucin 1 (MUC1) is a high-molecular-weight transmembrane glycoprotein that normally forms a protective, lubricated physical barrier on the apical surface of epithelial cells (NIH, 2021) [1.4.5]. In many cancers, particularly adenocarcinomas of the breast, pancreas, and lung, MUC1 is overexpressed and undergoes aberrant O-glycosylation due to the dysregulation of glycosyltransferases, leading to the exposure of truncated carbohydrate antigens such as the Tn antigen (GalNAcα1-O-Ser/Thr) (NIH, 2024) [1.3.1]. This specific glycoform, known as Tn-MUC1, acts as a tumor-associated carbohydrate antigen (TACA) and a neoantigen that is virtually absent in healthy tissues, making it a highly specific target for immunotherapy (Posey et al., 2016) [1.2.3]. Tn-MUC1 promotes tumor progression by facilitating cell-cell adhesion, enhancing metastatic potential, and mediating immune suppression through its interaction with the macrophage galactose-type lectin (MGL) on immune cells (NIH, 2016) [1.1.5]. Therapeutic strategies targeting Tn-MUC1 include chimeric antigen receptor (CAR) T-cells, antibody-drug conjugates (ADCs) like DS-3939, and glycopeptide vaccines designed to exploit its tumor specificity to induce targeted cell death or robust anti-tumor immune responses (ESMO, 2025; NIH, 2025) [1.3.5, 1.1.4].

Other names

Tumor-associated Mucin 1TA-MUC1MUC1-TnTn-glycoform of Mucin 1Cancer-associated Mucin 1Tn-MUC1 glycopeptide

Drugs targeting Tn-MUC1 utilize several mechanisms: CAR T-cell therapies (e.g., CART-TnMUC1) provide direct T-cell mediated cytotoxicity against cells expressing the Tn-glycoform (Posey et al., 2016) [1.2.2]; antibody-drug conjugates (e.g., DS-3939) deliver cytotoxic payloads specifically to tumor cells (ESMO, 2025) [1.3.5]; and monoclonal antibodies (e.g., Gatipotuzumab) induce antibody-dependent cellular cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC) (NIH, 2025) [1.1.4]. Additionally, glycopeptide vaccines aim to stimulate the adaptive immune system to produce tumor-specific IgG antibodies and activate CD4+/CD8+ T-cells (NIH, 2024) [1.1.1].