Federal Grant Award Summary

The University of Pennsylvania received a $1.625 million Project Grant from the National Heart, Lung, and Blood Institute (NHLBI) under the Cardiovascular Diseases Research program (CFDA 93.837), with an award date of May 1, 2026 and completion date of April 30, 2030. This grant funds the development of engineered chimeric antigen receptor T regulatory cells (CAR TRegs) as a novel immune-based cell therapy for heart failure associated with myocardial infarction. The research will generate CAR TRegs targeted to activated fibroblasts expressing fibroblast activation protein (FAP) through both ex vivo and in vivo approaches using targeted lipid nanoparticles to deliver modified messenger RNA (mRNA). The project also includes methods to "armor" CAR TRegs to enhance their anti-inflammatory functions, with the goal of accumulating these cells in fibrotic, damaged regions of the myocardium to suppress inflammation, promote healing, and improve cardiac function.

This grant represents a translational research initiative addressing a significant clinical limitation in post-infarction heart failure treatment. Unlike cytotoxic CAR T cell approaches that risk myocardial rupture by eliminating activated fibroblasts, CAR TRegs provide a non-cytotoxic alternative that suppresses inflammation and fibrosis while preserving structural integrity. The research will be conducted at the University of Pennsylvania's facility in Philadelphia, Pennsylvania, with deliverables expected to advance therapeutic options for a major cardiovascular disease indication through NHLBI's mission-focused support of basic, translational, and clinical cardiovascular research.