CAR-T Cell Therapy for Autoimmune Kidney Diseases: Where Do We Stand Now?

Autoimmune kidney diseases (AIKDs) are a consequence of the dysregulation of immune response and the loss of tolerance to self-antigens, which led to glomerulonephritis and tissue damage. Autoantibody-producing B cells, as well as T cells, neutrophils and macrophages play a pivotal role in the pathogenesis and progression of various AIKDs. In recent years, B cell-depleting/modulating therapies and molecules that modulate T cell differentiation pathways and cytokine production have become a new hope for patients with immune-mediated kidney diseases. However, these biologicals often do not bring satisfactory therapeutic benefits, which is most likely related to incomplete B cell depletion of tissue-resident B cells. A new hope is immunotherapy with chimeric antigen receptor (CAR) effector cells. In CAR therapy, immune cells (mostly T cells) are genetically modified to express a CAR, which enables the recognition of the specific antigen on a target cell. This interaction leads to the formation of immune synapse and cytotoxicity. CAR-based strategies are a potent form of cell therapy that offers a better chance for deep and durable response than other recently approved immune therapies. Moreover, CAR-T cells can be programmed for higher precision and safety. This review explores the current landscape of CAR-T cell therapy in AIKDs.