Mapping human cardiac-reactive T cells to engineer regulatory T cell-based immunotherapies

• Applicant: Antonino Cassotta, Ph.D.
• Subject Area: Cardiology, Angiology
• Term: since 2025
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 556213552

Heart diseases are the leading cause of death worldwide and the most common cause of hospitalization in Germany. Inflammation is now recognized as a major contributor to the pathogenesis of cardiovascular diseases. However, little is known about the molecular mechanisms of adaptive immune responses against the cardiac tissue in humans. Additionally, there is an urgent need for novel and precise strategies to diagnose, monitor, and treat cardiac inflammation. In this project, we aim to systematically identify cardiac autoantigens targeted by T cells isolated from the blood and cardiac tissue of patients experiencing sterile or non-sterile heart inflammation. The T cell receptor (TCR) sequences and cognate epitopes identified may lead to the definition of novel biomarkers of cardiotoxicity. Finally, we will leverage the newly identified cardiac-reactive TCRs to engineer novel TCR-transgenic regulatory T cell (Treg) cell-based immunotherapies to specifically suppress cardiac inflammation.

• DFG Programme: Emmy Noether Independent Junior Research Groups