biostudies-literatureChen KZNational Natural Science Foundation of China78https://www.ebi.ac.uk/biostudies/studies/S-EPMC12604166biostudies-literatureUnknown12(1)<h4>Background</h4>Tenascin-C (TNC) is an extracellular matrix (ECM) protein involved in tissue damage and fibrosis. Chimeric antigen receptor (CAR) cell therapy is a novel therapeutic approach that has attracted increasing attention in recent years. Here, we engineered CAR-macrophages targeting TNC (TNC-CAR-Ms) and explored the underlying mechanism through which TNC-CAR-Ms treat liver fibrosis.<h4>Methods</h4>The role of TNC in liver fibrosis was studied in established Tnc knockout (KO) and littermate control mice. A TNC-targeted single-chain variable fragment (scFv) was designed to generate TNC-CAR-Ms and evaluate their biological function. The phagocytosis and killing effects of TNC-CAR-Ms were tested in vitro, while the antifibrotic efficacy and safety of TNC-CAR-Ms were evaluated in vMilitary Medical ResearchTNC-targeted CAR-macrophage therapy alleviates liver fibrosis in mice.PMC126041668220450082072697Zhang WHuo YKZhou YXFu QMa XDZhang SSWan HYGao ZQLin ZYChen KZChen LJCheng HWfalseTNC-targeted CAR-macrophage therapy alleviates liver fibrosis in mice.<h4>Background</h4>Tenascin-C (TNC) is an extracellular matrix (ECM) protein involved in tissue damage and fibrosis. Chimeric antigen receptor (CAR) cell therapy is a novel therapeutic approach that has attracted increasing attention in recent years. Here, we engineered CAR-macrophages targeting TNC (TNC-CAR-Ms) and explored the underlying mechanism through which TNC-CAR-Ms treat liver fibrosis.<h4>Methods</h4>The role of TNC in liver fibrosis was studied in established Tnc knockout (KO) and littermate control mice. A TNC-targeted single-chain variable fragment (scFv) was designed to generate TNC-CAR-Ms and evaluate their biological function. The phagocytosis and killing effects of TNC-CAR-Ms were tested in vitro, while the antifibrotic efficacy and safety of TNC-CAR-Ms were evaluated in v2025-01-01T00:00:00Z2025 Nov2026-06-05T12:52:39.37Z2026-05-17T03:07:53.479ZS-EPMC126041664121483910.1186/s40779-025-00667-3