dual-targeting HER2 and PD-L1 CAR-T cells (Sichuan University)

Dual-targeting HER2 and PD-L1 CAR-T cells (also known as HER2.28ζ/PD-L1.BB CAR-T cells) is an investigational autologous cell therapy developed by Sichuan University for the treatment of HER2-positive solid tumors. The therapy consists of T cells engineered to co-express a second-generation chimeric antigen receptor (CAR) targeting Human Epidermal Growth Factor Receptor 2 (HER2) with a CD28 co-stimulatory domain, and a chimeric switch receptor (CSR) targeting Programmed Death-Ligand 1 (PD-L1) with a 4-1BB co-stimulatory domain. This design is intended to overcome the immunosuppressive tumor microenvironment by converting the inhibitory PD-L1 signal into a positive 4-1BB-mediated co-stimulatory signal, thereby enhancing the cytotoxic activity, proliferation, and persistence of the CAR-T cells. The product is currently being evaluated in a Phase I clinical trial (NCT04684459) across multiple HER2-positive indications, including breast, gastric, and ovarian cancers.

Other names

HER2/PD-L1 dual-targeting CAR-T