[Experiences after CD19-CAR T-cell therapy in non-SLE connective tissue diseases]

The treatment of fibrosing autoimmune diseases has so far shown no significant progress with respect to fibrosis. The reason for this is unclear. As in vitro and in vivo data have shown that B‑lymphocytes are not only responsible for autoantibody production but also play an important role in the activation of fibroblasts in an inflammatory event, depletion of B cells is meaningful in these fibrosing autoimmune diseases. The use of the CD20 antibody rituximab has shown some therapeutic benefits but could not decisively improve fibrosis, the prognosis-relevant complication in these diseases. This could be due to the insufficient tissue access of a soluble antibody and the resulting limited depletion of B‑lymphocytes in the inflammatory area of connective tissue. This is the decisive advantage of a cell-mediated destruction of autoimmune cells, which is possible via autologous B‑cell-directed chimeric antigen receptor (CAR) T‑cell therapy. The first data on the treatment of non-SLE connective tissue diseases with fibrosing aspects with autologous CAR T‑cells are developed based on this idea. This overview summarizes and discusses these data. It is important to coordinate research aspects of these experimental treatment approaches and the most important open questions, in our opinion, are proposed at the end of the review.