Preclinical scenario of targeting myocardial fibrosis with chimeric antigen receptor (CAR) immunotherapy - 13/01/23
Abstract |
Fibrosis is present in an important proportion of myocardial disorders. Injury activates cardiac fibroblasts, which deposit excess extracellular matrix, increasing tissue stiffness, impairing cardiac function, and leading to heart failure. Clinical therapies that directly target excessive fibrosis are limited, and more effective treatments are needed. Immunotherapy based on chimeric antigen receptor (CAR) T cells is a novel technique that redirects T lymphocytes toward specific antigens to eliminate the target cells. It is currently used in haematological cancers but has demonstrated efficacy in mouse models of hypertensive cardiac fibrosis, with activated fibroblasts as the target cells. CAR T cell therapy is associated with significant toxicities, but CAR natural killer cells can overcome efficacy and safety limitations. The use of CAR immunotherapy offers a potential alternative to current therapies for fibrosis reduction and restoration of cardiac function in patients with myocardial fibrosis.
Le texte complet de cet article est disponible en PDF.Graphical Abstract |
Overview of cardiac fibrosis treatments.
Current therapies for cardiac fibrosis are mainly focused on the modulation of fibrogenic cascade. New approaches based on immunotherapy have been develop to combat cardiac fibrosis. CAR T cell therapy has been used to recognize and kill the activated myofibroblasts in preclinical studies although in cancer, CAR T cells present several limitations such as Graft versus Host Disease (GvHD) or cytokine release syndrome (CRS). CAR NK therapy has overcome these limitations in cancer, although it has not yet been tested in myocardial fibrosis. Created with BioRender.com
Overview of cardiac fibrosis treatments.Current therapies for cardiac fibrosis are mainly focused on the modulation of fibrogenic cascade. New approaches based on immunotherapy have been develop to combat cardiac fibrosis. CAR T cell therapy has been used to recognize and kill the activated myofibroblasts in preclinical studies although in cancer, CAR T cells present several limitations such as Graft versus Host Disease (GvHD) or cytokine release syndrome (CRS). CAR NK therapy has overcome these limitations in cancer, although it has not yet been tested in myocardial fibrosis. Created with BioRender.comga1Le texte complet de cet article est disponible en PDF.
Highlights |
• | New therapeutic approaches are needed to treat cardiac fibrosis. |
• | CAR T cell immunotherapy has antifibrotic effect in cardiac fibrosis mouse models. |
• | CAR NK cells could be an “off-the-shelf” therapy that avoids CAR T cell toxicity. |
Keywords : Cardiac fibrosis, Immunotherapy, CAR T, Natural killer cells, CAR NK
Plan
Vol 158
Article 114061- février 2023 Retour au numéroBienvenue sur EM-consulte, la référence des professionnels de santé.
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