Key result
Anti-FAP bispecific T-cell engager reduces atherosclerotic plaque burden by targeting modulated vascular smooth muscle cells.
Why the study?
Vascular smooth muscle cell diversification drives atherosclerotic CAD, but the mechanisms governing these cell state transitions remain unclear.
Does an anti-FAP bispecific T-cell engager reduce plaque burden in atherosclerosis models?
Does an anti-FAP bispecific T-cell engager reduce plaque burden in atherosclerosis models?
Fibroblast activation protein (FAP) marks modulated vascular smooth muscle cells in atherosclerosis, and targeting it with a bispecific T-cell engager reduces plaque burden, highlighting a novel lipid-independent immunotherapeutic strategy.
Hypothesis-generating for FAP-targeted T-cell engagers in atherosclerosis; should not yet change clinical practice.
Vascular smooth muscle cell (VSMC) diversification drives atherosclerotic coronary artery disease (CAD). Mechanisms governing these cell state transitions remain unclear. We applied multiomic single-cell profiling, epitope mapping, and spatial transcriptomics across 27 human coronary arteries, identifying fibroblast activation protein (FAP) as a marker of modulated VSMCs. Lineage tracing in mice indicated that FAP + cells originate from Myh11 + VSMCs, and FAP PET imaging in CAD patients showed plaque uptake. FAP + cells states resided in the macrophage-rich neo-intima. Therapeutically, we developed an anti-FAP bispecific T-cell engager, which reduced plaque burden and remodeled the stromal–immune microenvironment through T-cell clonal expansion. Our study delivers a single-cell and spatial atlas of human CAD, establishes FAP as a marker of modulated VSMCs, and highlights immunotherapy for lipid-independent targets.
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Amrute et al. (2026) studied Atherosclerotic coronary artery disease (n=27). Anti-FAP bispecific T-cell engager was evaluated on Plaque burden and stromal-immune microenvironment remodeling. An anti-FAP bispecific T-cell engager reduced plaque burden and remodeled the stromal-immune microenvironment by targeting modulated vascular smooth muscle cells in atherosclerosis.
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