While previous studies have explored dual CAR or a costimulatory receptor (CCR) system to enhance cytotoxicity via increased avidity57,58,80, our study demonstrates that equipping CAR-T cells with a Tn-MUC1 binder and Tn antigen binder enables direct targeting of the cancer cell glycocalyx, significantly enhancing their efficacy in pancreatic cancer models in vitro and in vivo. Here, MUC1 is linked to familial pancreatic carcinoma.