Researchers from Memorial Sloan Kettering Cancer Center have developed a novel CAR T-cell therapy that targets the urokinase plasminogen activator receptor (uPAR) on supportive cells within the solid tumor microenvironment. This advancement addresses the longstanding challenge of CAR T-cell therapies, which have been largely ineffective against solid tumors due to their heterogeneous nature and protective microenvironments.
The study, published in Cell, reveals that uPAR is overexpressed in 12 of 14 human cancer types examined, with high levels correlating with mutations in key tumor-suppressor genes and pathways associated with aggressive cancer. This finding underscores the potential of uPAR as a therapeutic target, as the engineered CAR T-cells demonstrated efficacy in shrinking various solid tumors, including lung, pancreatic, and ovarian cancers.
In preclinical models, the uPAR-targeted CAR T-cells not only eliminated tumor cells but also disrupted the supportive fibroblasts and immunosuppressive myeloid cells that facilitate tumor growth. This innovative approach could enhance the effectiveness of existing treatments, particularly when combined with chemotherapy agents like cisplatin, and may lead to durable remissions in patients, marking a significant step forward in the fight against solid tumors.
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