A convergent uPAR-positive tumor ecosystem creates broad vulnerability to CAR T cell therapy - PubMed
8 hours ago
- #tumor microenvironment
- #solid tumors
- #CAR T therapy
- CAR T cell therapy is effective in blood cancers but limited in solid tumors due to antigen diversity and a fibrotic microenvironment.
- uPAR (urokinase plasminogen activator receptor) is identified as a target expressed in solid tumors with TP53/RAS mutations and in senescent stromal cells.
- Human uPAR CAR T cells can destroy both tumor and supportive stromal cells, leading to tumor regression and metastasis eradication in models.
- These CAR T cells work without causing long-term bone marrow suppression in humanized mouse models.
- Targeting uPAR with CAR T cells, especially combined with senescence-inducing treatments, offers a promising approach for broad solid tumor therapy.