CARdiac Immunotherapy: T Cells Engineered to Treat the Fibrotic Heart

Main Text Progressive tissue fibrosis underlies numerous disease states, where it can diminish healthy organ function and regeneration after injury.1 In the adult mammalian heart, excess fibrosis after myocardial infarction (MI) or in the setting of cardiomyopathy worsens cardiac function, leading to hypertrophy and, eventually, heart failure (HF),2 While there are no current therapies that directly address cardiac fibrosis, a recent study3 has demonstrated a potential new strategy that employs chimeric antigen receptor (CAR) T cells engineered to specifically ablate activated fibroblasts (myofibroblasts), reducing fibrotic burden in a mouse model of cardiac injury. Adoptive transfer of CAR T cells targeting tumor antigens, notably the B cell antigen CD19, has shown considerable promise in patients with blood or bone marrow malignancies, including acute lymphoblastic and chronic lymphocytic leukemias and non-Hodgkin’s lymphoma.10 Clinical trials are also underway to explore treatment of solid tumors with CAR T cell therapy, although the choice of surface antigen to mediate both selective and expansive malignant cell killing by CAR T cells remains problematic.7 However, if a suitable antigen is identified that is uniformly expressed, such as demonstrated on the surface of cardiac myofibroblasts in the study by Aghajanian et al.,3 CAR T cell therapy could be applied. [...]the recent findings of Aghajanian et al.3 represent an innovative and promising conceptual advance in treating cardiac fibrosis.