Inflammatory mediators play a crucial role in the development of heart failure (HF). Previous basic and clinical research has advanced the modern treatment of HF, however, its efficacy is still limited. Invariant natural killer T (iNKT) cells, a unique subset of T lymphocytes, play an important role in regulating tissue inflammation. We have demonstrated that the administration of α-galactosylceramide (α-GalCer), which specifically activates iNKT cells, could protect the heart against left ventricular (LV) remodeling and failure after myocardial infarction (MI). However, it activates iNKT cells temporarily and induces their anergy after repeated administration. In contrast, α-GalCer-pulsed human dendritic cells (α-GalCer/DC) can activate iNKT cells without inducing anergy even after repeated administration and have been investigated in the treatment of lung cancer.

To obtain α-GalCer/DC, peripheral blood mononuclear cells were separated from donors by apheresis, cultured with GM-CSF (800 U/mL) and IL-2 (100 U/mL) for 6 days, and pulsed with α-GalCer (100 ng/mL). Non-clinical studies have demonstrated that, similar to α-GalCer itself, intravenous administration of α-GalCer/DC (3.0×10⁶ cells, 1 and 4 days after the creation MI) into the MI mice could also efficiently activate iNKT cells and had a protective effect against LV remodeling and failure. Furthermore, they had no toxicity when administered to nude mice under the GLP standard. Now, we are planning Phase I/II clinical trial of iNKT cell-targeted therapy to determine its clinical safety and efficacy in HF patients on top of the standard pharmacological and non-pharmacological treatments.