This research identifies the urokinase plasminogen activator receptor (uPAR) as a vital target for CAR T cell therapy in solid tumors. While traditional treatments struggle with the fibrotic and immunosuppressive environment of tumors, uPAR CAR T cells effectively eliminate both malignant cells and the supportive stromal niche. These engineered cells show remarkable success in clearing primary and metastatic tumors in various preclinical models while maintaining a favorable safety profile. Furthermore, the study demonstrates that senescence-inducing therapies can increase uPAR expression, thereby boosting the treatment's antitumor efficacy. By dismantling the pro-fibrotic ecosystems that shield cancer, uPAR-directed therapy offers a promising strategy to overcome resistance in aggressive TP53-mutant diseases. These findings suggest that targeting uPAR could transform the landscape of solid tumor immunotherapy and chronic inflammatory conditions.

References:

• Zhang Z, Ho Y J, Fang X, et al. A convergent uPAR-positive tumor ecosystem creates broad vulnerability to CAR T cell therapy[J]. Cell, 2026.