CAR-T cell therapy for ANCA-associated vasculitis: Rationale, current evidence, and future directions

Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a relapsing, autoantibody-driven disease in which current therapies often fail to achieve durable remission or are limited by cumulative toxicity. Although CD20-directed B-cell depletion has transformed AAV management, persistent autoreactive B-cells and long-lived, tissue-resident plasma cells contribute to refractory disease and relapse. Chimeric antigen receptor (CAR) T-cell therapy offers a mechanistically distinct approach through deep and sustained depletion of pathogenic B-cell lineages and potential "immune reprogramming." Emerging clinical experience in autoimmune diseases, coupled with preclinical models and early case reports in AAV, has demonstrated rapid disease control, marked reductions in ANCA levels, and prolonged immunologic quiescence following CD19 CAR-T therapy. While safety signals in autoimmune populations appear favorable, critical questions remain regarding the durability of response, long-term immunologic consequences, optimal CAR constructs, and patient selection. This review summarizes the immunopathogenic rationale, existing evidence, safety considerations, and future directions for CAR-based therapies in AAV.