Dual-Action CAR T Cell Therapy Successfully Targets Both Solid Tumors and the Protective "Eco-System" that Shield Them

MSK researchers develop uPAR-targeting CAR T cells that eliminate solid tumors and their protective support tissues in lung, pancreatic, and ovarian cancer models.

By: AXL Media

Published: Mar 31, 2026, 4:24 AM EDT

Source: Information for this report was sourced from Memorial Sloan Kettering Cancer Center

Breaking the Barriers of Solid Tumor Immunotherapy

While CAR T-cell therapy has transformed the treatment of blood cancers, its application to solid tumors has been hindered by a lack of consistent targets and a hostile "microenvironment." Solid tumors often surround themselves with a dense network of scar tissue (fibrosis) and immunosuppressive cells that act as a physical and chemical shield against the immune system. To overcome this, MSK researchers have identified a new target: the urokinase plasminogen activator receptor (uPAR). By engineering T cells to seek out uPAR, scientists can now attack not just the cancer itself, but the entire biological infrastructure that allows the tumor to survive and spread.

Targeting the Tumor Ecosystem, Not Just the Cell

The primary innovation of uPAR-targeted CAR T cells is their ability to address cancer as an interconnected ecosystem. In healthy tissue, uPAR is rarely expressed, but it becomes highly active in cells stuck in a state of "constant wound healing"—a hallmark of both aggressive cancer cells and the supporting fibroblasts and myeloid cells that create the tumor's protective niche. Lead author Dr. Zeda Zhang notes that uPAR marks the broader environment that supports malignancy, setting it apart from previous targets that only focused on the cancer cells themselves. When the uPAR-positive support cells are eliminated, the tumor's "home" collapses, leaving it vulnerable to the immune system.

Success in Metastatic and Residual Disease Models

The effectiveness of this approach was demonstrated across several rigorous preclinical systems. In mouse models of ovarian cancer, the uPAR-targeting T cells successfully cleared widespread metastases and induced durable remissions. Remarkably, the mice that recovered showed a "memory" effect, resisting the development of new tumors when re-exposed to cancer cells later. Furthermore, the study found that a single dose of these engineered cells administered after surgery was significantly more effective at eliminating residual microscopic disease than surgery alone, which often only provides a temporary reprieve.