The Potential of CAR-T cells for Treating Heart Diseases: Current Status and Hurdles in Clinical Translation.

Abstract

Traditional treatments for heart disease, including pharmacotherapy and surgical interventions, are effective in managing symptoms and preventing complications but often fail to fully restore cardiac function or halt the progression of the disease. Additionally, these approaches are frequently associated with significant adverse effects. Inspired by the success of CAR-T cell therapy in oncology, this review examines the potential of CAR-T cell technology for treating heart diseases, detailing how CAR-T cells, engineered by merging antibody-derived targeting domains with T-cell signaling domains. The technology's core includes an extracellular antigen-binding domain, hinge region, transmembrane domain, and intracellular signaling domain, with the single-chain variable fragment (scFv) playing a crucial role in antigen recognition. The paper delves into the immune mechanisms in cardiovascular diseases like heart failure, hypertension, and myocardial infarction, focusing on the roles of T cells in promoting myocardial fibrosis and the therapeutic potential of regulatory T cells (Tregs) in recovery phases. Additionally, it explores the use of lipid nanoparticles (LNPs) carrying mRNA to produce transient, non-integrative CAR-T cells targeting fibroblast activation protein (FAP) to reduce myocardial fibrosis, a method showing promise in preclinical models by enhancing cardiac function and reducing ventricular fibrosis. Despite its potential, the study acknowledges challenges in clinical translation, such as limited therapeutic effects and severe inflammatory responses, highlighting the need for further optimization and research in CAR-T cell technology for cardiovascular disease treatment.