Pioneering CAR T Cell Therapy Blocks Plaque Buildup, Showing Promise Against Atherosclerosis

Nov 21, 2025— PHILADELPHIA — A groundbreaking preclinical study led by scientists at the University of Pennsylvania’s Perelman School of Medicine has demonstrated that CAR T cell therapy, a personalized form of immunotherapy previously used only for cancer, could be highly effective against atherosclerosis, the primary underlying cause of heart attacks and strokes.

The research, published today in the journal Circulation, showed that an experimental anti-inflammatory CAR T cell therapy reduced arterial plaque buildup in treated mice by approximately 70% compared to controls. This marks the first time CAR T cell technology has been used successfully to target the fundamental cause of the world’s leading cause of death.

Repurposing CAR T: Suppression, Not Attack

CAR T cell therapy typically involves engineering a patient’s own T cells to aggressively recognize and destroy cancer cells. For atherosclerosis, researchers engineered a different type of immune cell: regulatory T cells (Tregs), which are known to dampen the immune response and suppress inflammation.

• Targeting Inflammation: The team engineered a specialized CAR Treg to target oxidized LDL (OxLDL), the primary inflammation-stoking form of cholesterol that drives plaque formation in the arterial wall.

• Mechanism of Action: “The idea was, if we can get the immune system to see OxLDL and provoke an anti-inflammatory response, it would reduce inflammation and essentially stop the pathogenesis in its tracks,” explained lead author Robert Schwab, MD.

Atherosclerosis is driven largely by inflammation, but there are currently no approved treatments that specifically target this aspect of the disease. Co-author Daniel J. Rader, MD, noted that the CAR T approach could provide an “important complementary treatment” to existing cholesterol-lowering therapies.

70% Reduction in Arterial Plaque

The researchers confirmed that the engineered anti-OxLDL CAR Tregs were successful in suppressing inflammation in lab-dish tests using human cells.

They then tested a mouse version of the anti-OxLDL CAR Treg in mice genetically predisposed to high cholesterol and atherosclerosis. After about 12 weeks of treatment:

• The treated mice showed a roughly 70% lower atherosclerotic plaque burden in their hearts and aortas compared to control mice.

• This significant preventive effect was achieved without disrupting general immune function in the treated animals.

Senior author Avery Posey, PhD, emphasized the broad implications: “This preclinical finding represents an important step forward for continuing to expand the impact of CAR T cell therapy to common diseases beyond cancer.”

To continue development and move toward human clinical trials, the researchers and the University of Pennsylvania have founded a spinout company, Cartio Therapeutics. The therapy is envisioned as an additional tool for patients who require more than existing cholesterol and lifestyle treatments to manage their high residual risk of cardiovascular disease.