Work

CD248-targeted BBIR-T cell therapy against late-activated fibroblasts in cardiac repair after myocardial infarction

Year: 2025

Type: article

Abstract: Excessive cardiac fibrosis is a key cause of heart failure and adverse ventricular remodelling after myocardial infarction. The abnormally activated fibroblasts after scar maturation are the chief culprit. Single-cell RNA sequencing of mouse cardiac interstitial cells after myocardial infarction depicts a late-activated fibroblast subpopulation F-Act and initially identifies its characteristic antigen CD248, which is also verified in human hearts. On this basis, we develop a CD248-targeted BBIR-T cell therapy against F-Act to correct cardiac repair disorders. By embedding avidin coupled to the T cell signalling domain onto the membrane, T cells are empowered to recognize and kill target cells labelled by biotinylated antigen-specific molecules. The precise removal of F-Act after the scar matured effectively inhibits fibrotic expansion in the peri-infarct zone and improves cardiac function. This therapy provides a new idea for the treatment of cardiac fibrosis and also promotes the application of engineered T cells to non-tumour diseases.

Source: Nature Communications

DOI: 10.1038/s41467-025-56703-2