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A new preclinical study led by Robert Schwab and published in Circulation suggests that CAR T cell technology—best known for revolutionising cancer treatment—may also help combat coronary artery disease. Researchers at the University of Pennsylvania engineered a specialised form of regulatory T cell, known as a CAR Treg, designed to recognise oxidized LDL (OxLDL), a key inflammatory trigger that drives the development of atherosclerotic plaques.
The team created human and mouse Tregs programmed with a chimeric antigen receptor that targets an oxidation-specific epitope on OxLDL. These engineered cells retained their regulatory, anti-inflammatory behaviour, releasing calming immune signals and reducing foam-cell formation in lab experiments. When the mouse version of these CAR Tregs was tested in a hyperlipidaemic mouse model—a system that mimics human plaque formation—the treated animals developed around 70% less arterial plaque than untreated mice, all without impairing normal immune function.
This work builds on extensive research linking OxLDL to endothelial activation, macrophage recruitment, and plaque instability, as well as earlier findings that traditional Tregs can modestly counteract atherosclerosis. By directing regulatory T cells precisely toward OxLDL, the researchers may have found a way to intervene earlier and more effectively in the disease process.
Senior author Avery Posey notes that this is the first demonstration that CAR T cell engineering could be repurposed to treat the root causes of common non-cancer diseases like heart disease. The team now aims to test whether these CAR Tregs can shrink existing plaques, not just prevent new ones, and to assess their behaviour in more human-like systems. UPenn has already launched Cartio Therapeutics to advance this approach toward future clinical trials.
