CAR T cells therapy: a promising approach to treat cardiac fibrosis

Fibrotic diseases cause annually more than 800,000 deaths worldwide, of which the majority is provoked by lung and cardiac fibrosis. Cardiac fibrosis is a pathology characterized by an excessive accumulation of components of the extracellular matrix and it is involved in the stiffening of the matrix and cardiac functions abnormalities. A complex interconnection among different signaling pathways, including TGF-β signaling, Wnt signaling and the renin-angiotensin-aldosterone system, is the cause of the development of this pathology and of the lack of a drug on the market that primarily acts as anti-fibrotic. The main objectives of this thesis are to illustrate changes in genes expression occurring following the induction of fibrosis and to analyze a new therapeutic approach to treat cardiac fibrosis: CAR T cells therapy. McLellan and collaborators offer an insight of the cardiac cellulome and highlights molecular and cellular drivers of cardiac fibrosis to broaden the understanding of the pathological development, and so to clarify the network of connections that are responsible for the pathogenesis of fibrosis. Proceeding with the analysis of CAR T cells therapy, the works of Aghajanian and collaborators and of Rurik and colleagues investigate the efficacy of T cells associated with chimeric antigen receptors targeting FAP. The evidence from studies on CAR T cells targeting FAP define a promising approach that could revolutionize the clinical management of cardiac fibrosis. While further research is required before translating this therapy from murine models to human patients, these results mark an important step towards developing targeted therapies that could affectively act against cardiac fibrosis.