Chimeric antigen receptor (CAR) T-cell therapy is an impactful treatment for blood cancers, such as leukemia and lymphoma. However, the immunotherapy has struggled against solid tumors, as tumor cells often do not share one consistent surface target. Additionally, many solid tumors are protected by a dense network of scar tissue and immune-suppressive cells that block T-cells. To address these challenges, researchers from Memorial Sloan Kettering (MSK) Cancer Center have developed a new CAR T-cell that attacks supportive cells in the tumor microenvironment that bear the surface protein, urokinase plasminogen activator receptor (uPAR). The work is described in a new study published in Cell titled, “A convergent uPAR-positive tumor ecosystem creates broad vulnerability to CAR T-cell therapy.” Results showed that uPAR was elevated in 12 of the 14 human cancer types analyzed by the study. High uPAR expression was most strongly associated with mutations that compromise p53, the tumor-suppressor often called the ‘guardian of the genome,’ and activating mutations in KRAS and other genes in the RAS pathway. Additionally, strong uPAR levels were associated with the activation of genes that are important for cellular plasticity, inflammation, and fibrosis, which are all hallmarks of aggressive cancer. Scott Lowe, PhD, chair of the cancer biology and genetics program at MSK and co-corresponding author of the study, emphasized that the new uPAR targeting approach shrank several types of solid tumor in the lab, including lung, pancreatic, and ovarian cancers and even cleared metastases in some experiments. These engineered cells selectively eliminated solid tumor cells, and fibroblasts and immunosuppressive myeloid cells that…
