Umprogrammierte T-Zellen zur Behandlung der rheumatoiden Arthritis
摘要
Autoreactive T cells are considered culprits in etiology and progression of rheumatoid arthritis (RA). Most therapeutic approaches to RA, therefore, aim at suppressing the activation and proliferation of these immune cells. Here, we discuss how T cells can be used to generate precise and highly active therapies to treat RA and other autoimmune diseases. This sounds counterintuitive; however, novel therapies that override the specificity of T cells, which is determined by the T cell receptor (TCR) complex, can make T cells recognize a predetermined cell surface target antigen. T cells reprogrammed in this way can now eliminate with high efficiency B cells that carry the marker protein CD19. Principally, there are two kinds of such therapies: the use of bispecific antibody-based constructs (so-called T cell engagers, TCE) and the creation of genetically engineered T cells derived from the patient that bear an artificial chimeric antigen receptor (CAR‑T cells). While bispecific antibodies act as adaptors and can link any type of T cell to target cells, a patientʼs CAR‑T cells express a specific artificial chimeric receptor. In both cases, target cells are lysed with high efficiency and precision by the reprogrammed T cells. Using these two novel therapeutic approaches, compelling clinical responses were achieved in patients with advanced RA and other autoimmune diseases on the basis of deep B cell depletion. Both approaches will be presented, their differences will be explained, and the latest clinical experience and future development discussed.