Science translational medicineJan 21, 2026

New CAR T Cell Therapy Reduces Liver Scarring in Fatty Liver Disease

Updated Jan 24, 2026

Abstract

Liver scarring, or fibrosis, is a serious problem in liver diseases and is often caused by certain liver cells. This study investigates a new treatment using specialized CAR T cells that target these problematic cells in a common liver condition known as metabolic dysfunction-associated steatohepatitis (MASH). By generating these CAR T cells inside the body, the treatment was found to significantly lower fibrosis levels and improve liver function. The therapy works not only by attacking the fibrotic cells but also by positively influencing other types of liver cells, leading to overall healing of the liver. This research suggests that CAR T cell therapy could be a promising new approach for treating liver diseases with no current effective antifibrotic treatments.

Simplified

Hepatic fibrosis is a key predictor of mortality in liver disease, driven by fibrogenic hepatic stellate cells (HSCs). Targeting these fibrogenic cells may therefore offer a therapeutic approach for hepatic fibrosis. We previously showed that in vivo-generated chimeric antigen receptor (CAR) T cells targeting fibroblast activation protein alpha (FAP) reduced murine cardiac fibrosis. Here, we explored the antifibrotic potential of this in vivo-generated anti-FAP CAR T cell therapy in metabolic dysfunction-associated steatohepatitis (MASH), a highly prevalent disease with no approved antifibrotic therapies. We first established that FAP expression in both human and murine MASH is specific to HSCs. We then used flow cytometry, Sirius Red morphometry, digital pathology analysis, and single nuclear RNA sequencing to assess the impact of anti-FAP CAR T cell therapy on murine MASH. Anti-CD5-targeted lipid nanoparticles carrying anti-FAPCAR messenger RNA transiently generated activated anti-FAP CAR T cells, which substantially reduced fibrosis by depleting profibrogenic HSCs. They also modulated immune cells, endothelial cells, and hepatocytes in a non-cell autonomous manner to mitigate inflammation and restore hepatic homeostasis. These findings highlight the potential of in vivo CAR T therapy to attenuate a highly morbid and pervasive liver disease, not only by directly reducing fibrosis but also through indirect effects on other cell types.

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