Targeting modulated vascular smooth muscle cells in atherosclerosis via FAP-directed immunotherapy - PubMed
3 months ago
- #immunotherapy
- #vascular smooth muscle cells
- #atherosclerosis
- Vascular smooth muscle cell (VSMC) diversification is a key driver of atherosclerotic coronary artery disease (CAD).
- Fibroblast activation protein (FAP) was identified as a marker of modulated VSMCs through multiomic single-cell profiling and spatial transcriptomics.
- Lineage tracing in mice showed that FAP+ cells originate from Myh11+ VSMCs, and FAP PET imaging in CAD patients confirmed plaque uptake.
- FAP+ cell states were found in the macrophage-rich neo-intima.
- An anti-FAP bispecific T-cell engager was developed, reducing plaque burden and remodeling the stromal-immune microenvironment via T-cell clonal expansion.
- The study provides a single-cell and spatial atlas of human CAD and highlights immunotherapy for lipid-independent targets.