CD248-targeted BBIR-T cell therapy against late-activated fibroblasts in cardiac repair after myocardial infarction.
Summary
The study identifies a late-activated fibroblast population (F-Act) expressing CD248 during scar maturation and develops a CD248-targeted BBIR-T cell therapy. Precise depletion of F-Act after scar maturation curbs peri-infarct fibrotic expansion and improves cardiac function in mice, with CD248 expression verified in human hearts.
Key Findings
- Single-cell profiling revealed a late-activated, CD248+ fibroblast subset (F-Act) after MI; CD248 was also confirmed in human hearts.
- CD248-targeted BBIR-T cells selectively depleted F-Act after scar maturation, reducing peri-infarct fibrotic expansion and improving function.
- Therapeutic windowing (post-maturation targeting) indicates feasibility to spare early repair while mitigating chronic fibrosis.
Clinical Implications
Suggests a time-staged, precision stromal-immunotherapy approach for post-MI remodeling where late-activated fibroblasts are targeted to restrain scar expansion without disrupting early repair.
Why It Matters
Introduces a first-in-class engineered T-cell strategy to selectively ablate pathogenic fibroblast subsets after scar maturation, demonstrating functional benefit and translational feasibility.
Limitations
- Preclinical, with safety, off-target, and immunogenicity profiles yet to be fully evaluated
- Manufacturing and delivery logistics for cell therapy in cardiac indications remain challenging
Future Directions
Optimize targeting (affinity, dosing, timing), assess safety in large-animal models, and explore combinations with antifibrotic or immune-modulating agents.
Study Information
- Study Type
- Basic/Mechanistic study
- Research Domain
- Treatment/Pathophysiology
- Evidence Level
- V - Preclinical therapeutic development with single-cell–guided targeting
- Study Design
- OTHER