Hung H-C, Fan M-H, Wang D, et al. Effect of Chimeric Antigen Receptor T Cells Against Protease-Activated Receptor 1 for Treating Pancreatic Cancer. BMC Medicine. 2023; (doi: 10.1186/s12916-023-03053-9).
Researchers believe protease-activated receptor 1 (PAR1) may be a viable target for chimeric antigen receptor (CAR) T-cell therapy in patients with pancreatic ductal adenocarcinoma (PDAC). They designed CAR T cells to recognize and bind to PAR1, whose overexpression on tumor cells is linked to disease progression and unfavorable survival rates in PDAC. The engineered cells, underpinned by a human anti-PAR1 scFv monoclonal antibody, efficiently recognized and eradicated about 80% of human PDAC cells in vitro. In a xenograft murine model, adoptive transfer of PAR1CAR-T cells inhibited the tumorigenesis of PDAC. The approach was deemed not only effective but also safe, as PAR1CAR-T immunotherapy spared healthy PAR1+ cell lines in vitro and induced minimal on-target off-target effects in the xenograft model. While encouraged by the findings, scientists say additional research is needed to investigate clinical and systemic toxicity and to identify PDAC populations most likely to benefit from CAR T-cell therapy, among other unknowns.