Role of Chimeric Antigen Receptor-Expressing Cell Therapy in Immune-Mediated Kidney Diseases: A Review.

Abstract

Immune-mediated kidney diseases are characterized by an adaptive immune response directed against various self-antigens. B cells, as progenitors of autoantibody-producing plasma cells and as antigen-presenting cells, play a crucial role in the pathogenesis of these diseases. Despite significant advancements in B-cell-targeting therapies, relapses are common among patients. Evidence of insufficient B-cell depletion by monoclonal antibodies such as rituximab, and the inability to deplete plasma cells, suggest that a more robust and complete B-cell depletion may be necessary for immune-mediated kidney diseases. Chimeric antigen receptor (CAR)-expressing cell therapy has emerged as a promising option. In this approach, immune cells like T cells are genetically engineered to recognize specific markers on B cells. By leveraging T cells' natural ability to infiltrate tissues and their high-affinity target binding, this method enables a deeper clearance of B cells than is usually observed with B-cell depleting monoclonal antibodies. This review explores the potential of using B-cell depleting CAR-expressing cell therapy in the treatment of immune-mediated kidney diseases.