CAR-T cells generated in vivo for the targeted treatment of myocardial fibrosis

Nov 16, 2025International immunopharmacology

Using CAR-T cells made inside the body to target heart tissue scarring

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Abstract

FAP-CAR-T cells significantly alleviated myocardial fibrosis and improved cardiac function in a mouse model.

Chimeric antigen receptor T-cell therapy using CD3-targeted lipid nanoparticles was developed to treat myocardial fibrosis.
FAP-CAR-T cells selectively eliminated target cells with high fibroblast activation protein expression while showing minimal damage to normal cells.
The safety evaluation indicated that the molecular switch HuEGFRt could induce apoptosis of CAR-T cells in the presence of cetuximab.
Blood tests confirmed that no adverse reactions occurred in the mouse model after treatment with FAP-CAR-T cells.

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Myocardial fibrosis is an irreversible pathological consequence that occurs as various heart diseases progress to their end stages. Currently, no effective therapeutic strategies have been established in clinical practice for its management. The development of T-cell therapy offers promising and innovative opportunities for the treatment of myocardial fibrosis. In this study, we employed CD3-targeted lipid nanoparticles (LNPs) to efficiently deliver the designed chimeric antigen receptor (CAR) structure and the molecular switch HuEGFRt mRNA into T cells, thereby successfully constructing CAR-T cells targeting fibroblast activation protein (FAP). The experimental results demonstrated that FAP-CAR-T cells could specifically eliminate target cells with high FAP expression while exhibiting minimal cytotoxicity on normal cells. Furthermore, the in vivo-generated FAP-CAR-T cells significantly alleviated myocardial fibrosis and effectively improved cardiac function. Regarding safety evaluation, the introduced molecular switch HuEGFRt could selectively induce apoptosis of CAR-T cells via complement-dependent cytotoxicity (CDC) and antibody-dependent cell-mediated cytotoxicity (ADCC) in the presence of cetuximab. Blood routine and biochemistry test results confirmed that the in vivo-generated FAP-CAR-T cells did not elicit any adverse reactions in the mouse model. Therefore, the in vivo generation of FAP-CAR-T cells via LNPs targeting CD3 represents an effective and safe therapeutic strategy for treating myocardial fibrosis. This innovative method not only exhibits substantial therapeutic potential but also expands the clinical application prospects for patients with myocardial fibrosis.

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CAR-T cells generated in vivo for the targeted treatment of myocardial fibrosis

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