CD19 chimeric antigen receptor-T cell therapy in murine immune thrombocytopenia.

Immune thrombocytopenia (ITP) is an autoimmune disorder characterized by antiplatelet autoantibodies, with many patients refractory or relapsing on conventional treatments. GPIbα, an important autoantigen in ITP, is notably linked to refractoriness, highlighting the need for novel treatments. We assessed CD19 chimeric antigen receptor (CAR)-T cell therapy's potential in a modified murine model targeting GPIbα. CD19 CAR-T cell infusion accelerated platelet count recovery compared to the control group, effectively depleted CD19+ B cells and CD138+ plasma cells, and markedly reduced anti-GPIbα autoantibodies in vivo. In vitro CD19 CAR-T cells reduced both plasma cells and B cells in the spleens of mice and ITP patients. CD19 CAR-T cell therapy significantly altered T-cell subsets, increasing regulatory T cells, T helper 1 and T helper 17 populations, suggesting a role in modulating the immune response for sustained ITP remission. Monitoring of body/spleen weights and temperature showed no significant cytokine release syndrome, indicating a favourable safety profile. These promising results support the potential of CD19 CAR-T cell therapy as a novel treatment option for refractory ITP, particularly in GPIbα-positive autoantibody patients. Further clinical studies are warranted to assess the safety and efficacy of this approach in human patients.