glyco-bridge CAR-T cells

Glyco-bridge CAR-T cells are an advanced form of Chimeric Antigen Receptor (CAR) T-cell therapy engineered to improve efficacy against solid tumors, particularly pancreatic cancer. Traditional CAR-T cells often face challenges in solid tumor microenvironments due to antigen heterogeneity, immunosuppression, and physical barriers like the glycocalyx. These engineered CAR-T cells are equipped with a non-signaling glycan-binding receptor, termed a 'glyco-bridge', in addition to their primary CAR. The glyco-bridge is designed to bind to tumor-specific glycoforms, such as truncated MUC1 (Tn-MUC1) and the Tn antigen, which are often overexpressed in cancers like pancreatic cancer and contribute to the mucin barrier. By binding to these glycans, the glyco-bridge enhances CAR-T cell adhesion, infiltration into the tumor, and activation of the CAR signaling pathway, thereby overcoming physical barriers and improving tumor control and overall survival in preclinical models. The glyco-bridge itself does not directly initiate cytotoxicity but rather facilitates the CAR-T cell's interaction with and function against target cells. Initial designs utilized a Tn-MUC1 scFv, and later tandem Helix pomatia agglutinin (HPA) lectins were incorporated into the non-signaling glyco-bridge to enable broader recognition of the Tn antigen while mitigating on-target/off-tumor toxicity observed with HPA-based CAR-T cells.

Other names

MSLN-targeted CAR-T cells with Tn-MUC1 glyco-bridgeTn-MUC1 glyco-bridge CAR-T cellsTn-MUC-1 glyco-bridge CAR-T cellsTn-MUC 1 glyco-bridge CAR-T cells