Tumor-associated truncated core 1 O-glycan (Truncated core 1 O-glycan)

Tumor-associated truncated core 1 O-glycans, including the Tn and Thomsen-Friedenreich (TF) antigens, are aberrant carbohydrate structures resulting from incomplete O-glycosylation in malignant cells, often due to the loss of function of the C1GALT1 enzyme or its chaperone COSMC (Nature, 2018). While these glycans are hallmark features of many adenocarcinomas, such as colorectal and pancreatic cancers, their expression on specific immune subsets, such as naïve regulatory T cells (Tregs), has emerged as a significant factor in the immunosuppressive tumor microenvironment (Precision Biologics, 2024). On Tregs, these truncated glycans can alter cell signaling and suppressive capacity, contributing to the evasion of anti-tumor immune responses. Therapeutic strategies targeting these glycans include monoclonal antibodies like NEO-201, which are designed to recognize the truncated core 1 O-glycan epitope. By targeting these glycans, the antibody mediates direct tumor cell lysis via ADCC and selectively depletes highly suppressive naïve Tregs, thereby enhancing the efficacy of cancer immunotherapies like checkpoint inhibitors. This dual-action approach aims to both reduce tumor burden and restore a more robust anti-tumor immune environment.

Other names

Naïve regulatory T cells expressing tumor-associated truncated core 1 O-glycansNEO-201 antigenTn antigenThomsen-Friedenreich antigenTF antigenCore 1 O-glycanGalNAc-alpha-Ser/Thr

Monoclonal antibodies such as NEO-201 target truncated core 1 O-glycans expressed on the surface of tumor cells and specific immune subsets. These antibodies mediate anti-tumor activity through antibody-dependent cellular cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC). A key mechanism for NEO-201 is the selective depletion of naïve regulatory T cells (Tregs) that express these glycans, which reduces immunosuppression in the tumor microenvironment and enhances the efficacy of other immunotherapies like PD-1/PD-L1 inhibitors (Precision Biologics, 2024; AACR, 2024).