Engineered immunosuppressive and fibrosis-targeted dendritic cells expressing a chimeric antigen receptor (CAR)-like construct (iCDCs) protect against pathological cardiac remodelling in animal models of ischaemic and pressure-overload-induced heart failure, including a non-human primate model of myocardial infarction, according to research published in Nature. The study shows that the iCDC therapy reduces inflammatory cardiac fibrosis, improves cardiac perfusion and preserves contractility without inducing systemic toxicity. “The one-cell-type therapy product led to the induction of heart-specific regulatory T (Treg) cells to maintain long-term immune tolerance in the heart for functional recovery and reversal of fibrosis,” highlights Yang Xu, one of the senior authors of the study. “To our knowledge, this is the first immune approach that can induce a long-term beneficial effect by inducing endogenous Treg cells, a unique function of dendritic cells.”

Pathological cardiac remodelling after ischaemic or haemodynamic stress is a central contributor to loss of contractile function, irreversible myocardial damage and progression to heart failure. This maladaptive remodelling is characterized by interstitial fibrosis; however, at present, no approved therapies effectively prevent or reverse cardiac fibrosis. In this context, chronic inflammation in the heart has been shown to be a driver of cardiac fibrosis, but strategies to rebalance injurious versus reparative immune responses in the myocardium without systemic immunosuppression are still lacking.