HPA×2 CAR-T

HPA×2 CAR-T is an experimental chimeric antigen receptor (CAR) T-cell therapy featuring a tandem Helix pomatia agglutinin (HPA) lectin-based binding domain. Developed by researchers at Massachusetts General Hospital and Harvard Medical School, it is designed to target cancer-associated glycans, specifically the Tn antigen (GalNAc-Ser/Thr), which is frequently overexpressed in solid tumors such as pancreatic cancer. In preclinical studies, the HPA×2 configuration was identified as the most effective signaling design among various tandem repeats, demonstrating enhanced avidity and cytotoxicity against mucin-rich tumor cells. However, due to on-target, off-tumor toxicity observed in vivo, the HPA domain was subsequently utilized as a non-signaling glyco-bridge component in later iterations to improve the physical access of other antigen-specific CARs to the tumor cell surface.

Other names

tandem HPA-based CAR-T cells