Development of CAR Exosomes Targeting FAP for the Treatment of Intrauterine Adhesion.

Abstract

Engineered extracellular vesicles (EVs) have emerged as promising cell-free platforms for immunomodulation and tissue repair. In this study, we generated EVs derived from chimeric antigen receptor (CAR) T cells targeting fibroblast activation protein (FAP) and investigated their biological and therapeutic functions. These FAP-CAR EVs effectively inhibited intrauterine fibrosis, promoted endometrial regeneration, and increased pregnancy rates in a mouse model of intrauterine adhesion. Importantly, the exosome-based therapy did not affect embryonic development or trigger systemic inflammation, indicating high safety compared with T-cell-based treatment. Mechanistically, while FAP-targeted T cells could suppress fibrosis, they also induced severe cytokine-release toxicity, which was completely avoided in the EV-based strategy. Together, these findings demonstrate that FAP is a critical target for fibrotic disease intervention and that CAR-T-derived EVs represent a safe and effective vesicle-based therapeutic modality.