Immunotherapy in the Context of Aortic Valve Diseases

Aortic valve disease (AVD) affects millions of people around the world, with no pharmacological intervention available. Widely considered a multi-faceted disease comprising both regurgitative pathogenesis, in which retrograde blood flows back through to the left ventricle, and aortic valve stenosis, which is characterized by the thickening, fibrosis, and subsequent mineralization of the aortic valve leaflets, limiting the anterograde flow through the valve, surgical intervention is still the main treatment, which incurs considerable risk to the patient.

Though originally thought of as a passive degeneration of the valve or a congenital malformation that has occurred before birth, the paradigm of AVD is shifting, and research into the inflammatory drivers of valve disease as a potential mechanism to modulate the pathobiology of this life-limiting pathology is taking center stage. Following limited success in mainstay therapeutics such as statins and mineralisation inhibitors, immunomodulatory strategies are being developed. Immune cell therapy has begun to be adopted in the cancer field, in which T cells (chimeric antigen receptor (CAR) T cells) are isolated from the patient, programmed to attack the cancer, and then re-administered to the patient. Within cardiac research, a novel T cell-based therapeutic approach has been developed to target lipid nanoparticles responsible for increasing cardiac fibrosis in a failing heart. With clonally expanded T-cell populations recently identified within the diseased valve, their unique epitope presentation may serve to identify novel targets for the treatment of valve disease.

Taken together, targeted T-cell therapy may hold promise as a therapeutic platform to target a multitude of diseases with an autoimmune aspect, and this review aims to frame this in the context of cardiovascular disease, delineating what is currently known in the field, both clinically and translationally.