Tn-MUC1 glyco-bridge

The Tn-MUC1 glyco-bridge is a preclinical, non-signaling protein binder construct designed to enhance the efficacy of CAR-T cell therapies against solid tumors. Described in a 2025 *Nature Communications* publication, this construct is specifically engineered to target Tn-MUC1, a cancer-associated glycoform of the MUC1 protein characterized by the presence of the Tn antigen (N-acetylgalactosamine). When incorporated into CAR-T cells (such as those directed against mesothelin), the glyco-bridge acts as an auxiliary anchor, bridging the CAR-T cell to the tumor cell via the Tn-MUC1 glycan. This interaction increases the overall binding avidity and facilitates CAR activation in a density- and affinity-dependent manner, thereby improving tumor recognition and cytotoxicity in adenocarcinomas like pancreatic cancer where Tn-MUC1 is frequently overexpressed.