Scientists at the University of Pennsylvania in the United States have shown the great potential of a cancer immunotherapy for treating heart disease, a major study published today in nature, a leading academic journalUsing genetically modified immune cells, the researchers helped mice with high blood pressure heart disease restore heart functionThis result provides a proof of concept for the development of immunotherapy for heart diseasetalking about CAR-T cells, many people know it as a new treatment for the rapid rise of the cancer fieldSimply put, the principle of this treatment is to completely destroy cancer cells by genetically engineering them to install cancer patients' immune T cells with "chimed antigen receptors" (CAR) that identify cancer cellsCAR-T cell therapy has been approved by the U.SFood and Drug Administration (FDA) for the treatment of some leukemia syllamy and lymphoma, with excellent results" using patients' own cells to fight cancer is one of the most promising research breakthroughs of the past decade." Professor Jonathan Epstein, the study's author, said: However, as a world-renowned cardiologist, his interest in CAR-T cell therapy is different from others: "What excites us is that we can use the same type of technology to solve a wide range of other common diseases"
heart disease is one of the most common diseasesIn many types of heart disease, patients often develop a condition called cardiac fibrosis, which causes scarring in the heartExcessive myocardial fibrosis leads to a decrease in heart elasticity, which affects the blood supply function of the heart, and is an important cause of cardiovascular disease and death, however, there is currently no direct treatment for excessive cardiomyopathy, and there are few interventions that can improve heart function in such patientsteam led by Professor Epstein tried to fill the gap with CAR-T cell therapyIn terms of the causes of myocardial fibrosis, it is the important cells that make up the heart - fibroblasts that are activated after chronic inflammation or damage to the heart, resulting in extracellular matrix depositionIf activated heart fibroblasts are removed, heart stiffness can be alleviatedcardiomyocyte (Photo: References)followed this line, and the research team began designing engineered T-cells that target and remove activated fibroblastsfirst step, the researchers began proof-of-concept on mouse modelsUsing genetic methods, they allowed mice's heart muscle to form fibroblasts to express an artificial antigenAfter treatment with reagents, the mice showed symptoms similar to those caused by high blood pressure, including left ventricular hypertrophy, contraction and diastolic dysfunction, and multiple cardiomyopathy, the team then processed a group of mice with engineered T cellsThe surface of these T-cells has corresponding receptors, which theoretically can specifically target fibroblasts that express artificial antigensAfter 4 weeks, the mice who received "treatment" showed significantly less heart fibrosis than the contrasttestthee the feasibility of this strategy, the researchers began looking for proteins that are truly activated into specific expressions of fibroblasts as targets for cell therapyTo do this, they first used rna sequence databases to analyze significant differences in gene expression between heart patients and healthy human heart fibroblasts, and identified a candidate target protein: fibroblast activation protein (FAP)the significantly higher expression of FAP protein in the heart (Picture Source: References) in patients with hypertrophic cardiomyopathy (HCM) and Extended Cardiomyopathy (DCM), using the same principles as anti-cancer CAR-T cells, the researchers designed T cells to target FAP CAR-T cells, which were infused twice into mice with hypertensive heart diseasetreatment results are very obvious! The modified CAR-T cells recognize FAP proteins and significantly reduce myocardial fibrosisNot only that, but the contraction and diastolic function of the mice's heart improved over a four-week periodFAP CAR-T cells target cardiomyopathy (Photo: References1)"Our results suggest that engineered T-cells may not only be used to treat cancer, but may also expand into an effective treatment for heart disease." Lead author DrHaig Aghajanian concluded Although safety has been tested in mouse models from cytokine levels, expression of myocardial-related genes, and so on, the authors note that more needs to be done to minimize safety risks before treating human heart disease and to determine whether the protein identified in this study is the best therapeutic target in any case, this pioneering study offers us a broad perspective on the future of emerging immunotherapy in the treatment of heart disease, and we look forward to the results of follow-up studies References s1) Haig Aghajanian et al., (2019) Targeting cardiacsis with engineered t cells Nature DOI: 10.1038/s41586-019-1546-z Svenja Hinderer, Katja Schenke-Layland (2019) Cardiacsis - A Short review of the cause and the strategies Advanced Drug Delivery Reviews CAR T-Cell The Sydd May Harness ed to Treat Heart Disease Retrieved Sep 12, 2019
