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.
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.
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.
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.