Safety and Efficacy of FAP iCDC in Ischemia Cardiomyopathy

Ischemic heart disease (IHD) is becoming an increasingly serious global public health challenge due to its rising prevalence and the continuous increase in human life expectancy. Despite substantial advances in reperfusion therapy, pharmacological treatment, and risk factor management in recent decades, the clinical prognosis remains poor. A large proportion of patients continue to experience adverse cardiac remodeling after the initial ischemic injury, eventually progressing to heart failure. This persistent "residual risk" suggests that current therapeutic strategies do not fully address key pathogenic mechanisms underlying disease progression. In particular, inflammation plays a central role in linking acute myocardial injury to chronic cardiac remodeling. Dendritic cells (DCs), as professional antigen-presenting cells, function at the interface between innate and adaptive immunity and play a critical role in coordinating immune responses within the tissue microenvironment. Recent advances in the study of tolerogenic dendritic cells (tolerogenic DCs) have provided new insights into their potential application in cardiovascular diseases. Unlike conventional immunostimulatory DCs, tolerogenic DCs can induce antigen-specific immune tolerance through multiple mechanisms, including the secretion of regulatory cytokines, expression of co-inhibitory ligands, suppression of effector T-cell responses in an antigen-specific manner, and induction of regulatory T cells. These properties make DCs a promising yet underexplored platform for immune modulation. Based on this concept, we have developed a novel therapeutic strategy using engineered dendritic cells with immunoregulatory and lesion-targeting properties, termed immunoregulatory and lesion-targeted dendritic cells (iCDC). This approach aims to deliver engineered DCs to sites of cardiac injury, thereby modulating the balance between injurious and reparative immune responses. By targeting local immune regulation at the site of injury, this strategy may help attenuate adverse cardiac remodeling while potentially avoiding the systemic immunosuppression associated with conventional therapies.