Engineered 'triple-threat' immune cells could fight plaque buildup that causes heart attacks and strokes

A UCLA research team has developed a new type of immune cell called FAP.CAR-NKT cells, which are designed to combat atherosclerotic plaques—the fatty buildup in artery walls that leads to most heart attacks and strokes. These engineered cells recognize three harmful cell types within plaques: rogue smooth muscle cells, macrophages, and foam cells.

In a mouse model, lab-grown mini blood vessel tissue, and artery tissue from patients with severe heart disease, FAP.CAR-NKT cells consistently performed better than single-target versions, clearing out more of the multiple cell types that keep plaques active and dangerous. Atherosclerosis is a leading cause of death worldwide, and current treatments are limited due to plaques' complex environment packed with various cell types.

CAR-T cell therapy has shown promise in scarring-related diseases but has a drawback: targeting only one marker leaves other damaging cell types untouched. To overcome this limitation, UCLA scientists created FAP.CAR-NKT cells, which combine the targeting of rogue smooth muscle cells with natural receptors for macrophages and foam cells, and built-in sensors to detect stress markers from unhealthy foam cells.

In tests across three settings, FAP.CAR-NKT cells outperformed FAP.CAR-T cells, reducing plaque-associated cells and plaque burden more effectively while showing no signs of toxicity in mice. However, the durability and proper dosing of this treatment remain to be established.