The Achilles heel of the myeloid leukemia agudaPrimer patient with acute myeloid leukemia cured by immunotherapy T CAR
immunotherapy with T-cell CAR, which uses the own cells of patients to treat certain types of cancer, it may be a viable treatment option for other diseases deadly: the cardiac pathology.
The first study that has tested this idea, published today in “Nature”, researchers from the University of Medicine of Pennsylvania (USA) have employed T cells genetically modified to attack and eliminate a cell type – fibroblasts – activated that contribute to the development of cardiac fibrosis, a scarring process that is found in most of the pathologies of the heart and that causes stiff heart and decrease heart function. The team found that the approach significantly reduced cardiac fibrosis, and restored heart function in mice with heart disease caused by high blood pressure.
“The ability to take advantage of the own cells of the patients to fight cancer has been one of the research advances more promising of the last decade; now, we are excited to find a way to take advantage of this same technology to address other diseases,” says the study’s author, Jonathan A. Epstein.
And, while acknowledging the need to do a lot more research before we can introduce this approach in the clinical environment, highlights that “this marks an important step forward in our efforts to treat and, potentially, reverse a disease which accelerates the progression of heart failure”.
The ability to take advantage of the own cells of the patients to fight cancer has been one of the research advances more promising of the last decade
heart disease is The leading cause of death worldwide and the cardiac fibrosis is an important factor in the progression of many forms of heart disease. Develops after a chronic inflammation, or injury to the heart, where cardiac fibroblasts, cells that play an important role in the structure of the myocardium, the muscle layer half of the wall of the heart, are activated and start to remodel the myocardium by the deposition of the extracellular matrix.
research has shown that the elimination of cardiac fibroblasts activated can reduce the stiffness of the heart, which facilitates the relaxation of the ventricles . However, there are no therapies that target directly to the excessive fibrosis and very few interventions have demonstrated the ability to improve cardiac function and outcomes among patients with heart failure.
The therapy with T-cell CAR, which involves genetically modifying the own T-cells of a patient to combat diseases, is mainly used to treat cancers of the blood, including the types of lymphoma, and leukemia.
therapy with T-cell CAR, which involves genetically modifying the own T-cells of a patient to combat diseases, is mainly used to treat cancers of the blood, including the types of lymphoma, and leukemia.
Driven by the recent advances in the treatment of cancer, this team of researchers sought to determine the feasibility of the use of the approach of T-cell CAR to aim and attack the cardiac fibroblasts are activated that contribute to fibrosis.
As a first step, conducted a proof-of-concept genetics using mice that can express an artificial antigen (OVA) in cardiac fibroblasts.
mice were treated with agents for modeling heart disease hypertensive, a condition associated with left ventricular hypertrophy (enlargement or thickening of the walls of the heart), systolic and diastolic dysfunction (pumping of blood into and out of the heart) and cardiac fibrosis generalized.
To select selectively to the protein OVA-expressing cardiac fibroblasts, the team treated a cohort of mice with CD8 + T cells engineered to express a receptor for cognate T cells against the peptide OVA. At four weeks, the mice that were treated with cells re-showed less cardiac fibrosis, while mice in the control groups still had fibrosis and widespread.
After establishing the feasibility of this approach, the researchers sought to identify a protein specifically expressed by activated fibroblasts, so that they could program the T cells genetically modified to recognize and attack. Using a database of RNA sequences, the team analyzed the gene expression data of patients with heart disease and identified the target: the protein activation of fibroblasts (FAP), a glycoprotein of the cell surface. Then
next, the researchers transferred T cells CAR FAP designed to mice on the brands of one and two weeks, with the goal of targeting and depleting the cardiac fibroblasts that express FAP. In a month, l I researchers observed a significant reduction of the cardiac fibrosis in mice that were treated with cells modified s, as well as improvements in diastolic function and systolic.
The findings suggest that this approach can be extended beyond cancer and serve as an effective treatment for heart disease
“We have seen a tremendous progress in the treatment of certain types of cancer through the use of modified T cells. Our findings suggest that this approach can be extended beyond cancer and serve as an effective treatment for heart disease,” says first author Haig Aghajanian.
