Researchers have identified uPAR (urokinase plasminogen activator receptor) as a promising target for enhancing CAR T cell therapies aimed at treating solid tumors. Traditionally, CAR T therapies have excelled in hematological malignancies, particularly leukemia, but have struggled to adapt to the complex microenvironments of solid tumors. This study demonstrates that by focusing on uPAR-expressing cells—which are prevalent in the tumor microenvironment and associated with senescent cells—CAR T therapies can effectively target and eliminate cancer cells in various solid tumor models.

The findings reveal that uPAR is significantly upregulated in 12 out of 14 cancer types analyzed, with particularly high expression in ovarian, pancreatic, colon, lung, and brain cancers. This elevated expression presents a unique opportunity to target not just tumor cells but also the supportive stromal cells that contribute to tumor progression and immune suppression. In preclinical models, uPAR-targeted CAR T cells demonstrated robust efficacy in killing cancer cells, especially when combined with senescence-inducing agents like cisplatin, which further increased uPAR levels and enhanced the CAR T cells’ ability to attack tumor cells. Notably, in a mouse model of ovarian cancer, these engineered T cells successfully eradicated metastases and conferred long-term protection against tumor reoccurrence.

The implications of this research are substantial, as it shifts the paradigm for CAR T cell therapy from a focus on specific cell types to targeting a functional state of cells within the tumor microenvironment. This approach could expedite the development of CAR T therapies for solid tumors, potentially leading to more effective treatment regimens and improved patient outcomes. As uPAR-targeted strategies gain traction, they may also inform future therapeutic combinations and enhance the overall efficacy of cancer treatments.

Source: fightaging.org