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

Excessive cardiac fibrosis is a key cause of heart failure and adverse ventricular remodeling 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 biotin-binding immune receptor T cell therapy against F-Act to correct cardiac repair disorders. In our study, 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 an idea for the treatment of cardiac fibrosis and also promotes the application of engineered T cells to non-tumor diseases. Abnormal activation of fibroblasts in mature scars after myocardial infarction is a key etiological factor in tissue repair disorders. Here, the authors developed a BBIR-T cell therapy that precisely targets pathogenic fibroblast subpopulations, thereby delaying ventricular remodeling and deterioration of cardiac function.