Tiny warriors, big impact: targeted immunotherapy in kidney diseases

Recent advances in immunotherapy targeting B cells have ushered in a new era for disease treatment. The effectiveness of targeted approaches such as T-cell engagers or B cell-directed chimeric antigen receptor (CAR)-T-cell therapy in treating autoimmune diseases has been demonstrated so far only in uncontrolled, investigator-initiated trials. Several case series in patients with therapy-resistant systemic lupus erythematosus showed efficacy and safety of CD19⁺ CAR-T cells, showing depletion of autoreactive B cells and full clinical remission. Autoreactive B cells not only mediate pathogenesis of systemic lupus erythematosus and lupus nephritis, but also many other inflammatory kidney diseases such as antineutrophil cytoplasmic antibody-associated vasculitis, membranous nephropathy, and IgA-associated nephropathy. Moreover, many patients do not respond to currently used treatment options, resulting in a high rate of disease progression or recurrence. Thus, implementing novel B cell-targeting immunotherapies in kidney diseases could lead to a more effective depletion of autoreactive B cells and sustained suppression of autoimmunity than conventional anti-CD20 antibody therapy. However, data on the application of these approaches in kidney diseases remain limited. Therefore, it is important to investigate their effects on clinically relevant kidney endpoints, such as proteinuria reduction, stabilization of estimated glomerular filtration rate, histologic improvements, and rates of disease remission, particularly in the context of autoimmune kidney diseases. This review provides a summary of kidney-specific applications and side effects associated with novel immunotherapies, including allogeneic and autologous CAR-T cells and T-cell engagers, and offers a perspective on emerging immunotherapeutic approaches.