Engineered T regulatory cells to control the immune-inflammatory response and the accelerated onset of atherosclerosis in familial hypercholesterolemia

Familial hypercholesterolaemia (FH) is a dominantly inherited condition and is generally fully penetrant. Affected individuals typically have elevated LDL-Cholesterol levels which are associated, if untreated, with symptomatic coronary disease and premature death. The management of FH is limited by the serious side effects of the high doses of the available therapies. Recent data indicate that FH patients could present a local and systemic highly activated and pro-inflammatory committed immune system, probably as a consequence of defective tolerance and increased reactivity to LDL. This project will investigate the benefits of a new strategy in the inherited conditions of hypercholesterolemia. A subset of T-regulatory lymphocytes genetically manipulated to constitutively express the CCR2 receptor (CCR2-Treg) will be generated. These cells will have the capability to be selectively recruited in the atherosclerotic plaque, dampen the immune response and improve the outcome in genetically driven hypercholesterolemia.