A SAHZU research team has developed an engineered dendritic cell‑based immunotherapy that reduces cardiac fibrosis and improves heart function in preclinical models of heart failure. The findings were published online in Nature.

Heart failure affects an estimated 64 million people globally. For patients with advanced disease, treatment options remain limited, and the one‑year mortality rate for end‑stage heart failure in China can reach 50%.

The team, led by cardiologist Prof. HU Xinyang and immunologist Prof. XU Yang, engineered dendritic cells (DCs) to home to the injured heart and establish local immune tolerance. The approach addresses the chronic, maladaptive immune activation that drives cardiac remodeling and fibrosis after myocardial injury.

How the therapy works

The researchers modified DCs in two key ways. First, they expressed a single‑chain antibody targeting fibroblast activation protein (FAP), which is highly expressed in damaged heart tissue. This allows the cells to accumulate specifically in the injured heart rather than circulating systemically. Second, they engineered the DCs to co‑express three immunosuppressive factors: PD‑L1, CTLA‑4, and interleukin‑10.

Once localized to the heart, the engineered DCs (termed iCDCs) suppress overactive immune cells and pro‑fibrotic stromal cells, while expanding protective regulatory T cells (Tregs). This creates a stable immunotolerant microenvironment that limits fibrosis and supports cardiac repair.

Preclinical results

In multiple mouse models—including ischemia‑reperfusion, myocardial infarction, and pressure overload—the iCDC treatment reduced cardiac fibrosis, improved local perfusion, and enhanced systolic function. Survival rates also improved. The therapy's efficacy and safety were further validated in a non‑human primate model of myocardial infarction.

Future potential

If successfully translated to clinical use, this approach could offer a new class of treatment for millions of heart failure patients worldwide. Unlike conventional anti-inflammatory drugs that carry risks of systemic immunosuppression, iCDCs are designed to act locally within the damaged heart, potentially reducing side effects. The therapy could complement existing medications and devices, and may be applicable to other conditions driven by pathological fibrosis and chronic inflammation.

"This is the first time that targeted immune modulation using engineered dendritic cells has been applied to heart failure," said Pro. HU. The strategy represents a potential new direction beyond conventional drugs or device-based therapies.

The team is now working to scale up clinical-grade iCDC production and plans to advance the therapy toward human trials.