CAR-T cells targeting CD19 for the treatment of ANCA vasculitis

Autoimmune ANCA-associated vasculitis (AAV) and glomerulonephritis is characterized by the presence of autoantibodies (so-called ANCA = anti-neutrophil cytoplasmic autoantibodies), which, by binding to the body's own antigens, lead to damaged blood vessels (vasculitis) and subsequently to organ damage, particularly of the kidneys. The primary endogenous antigens are the enzymes proteinase 3 (PR3) and myeloperoxidase (MPO) expressed by neutrophil granulocytes and monocytes. In addition to the autoantibodies, both T-cellular response to those autoantigens and monocyte/macrophage-mediated processes play a decisive role. Since conventional therapy is based on the widespread suppression of the immune system, susceptibility to infections or the development of cancer are possible side effects. Furthermore, not all patients respond to conventional therapy or despite responding first suffer multiple relapses. Therefore, there is a need for alternative treatment strategies and one promising option is the use of CD19-targeting CAR-T cells.