Looking forward, Dr. Jackson stated that he believes that the field will explore multiple avenues of CAR T cell therapy. Initial work has used autologous CAR T cells, but Dr. Jackson pointed out the potential utility of using allogenic CAR T cells. Scientists are also pursuing such work as engineering natural killer cells instead of T cells (CAR NK), generating CAR T cells and NK cells from induced pluripotent stem cells, finding ways to deliver CAR T in vivo (without removal of the patient’s T cells) and using T cell engagers, a kind of bispecific monoclonal antibody.
Dr. Jackson said that most CAR T cell trials in SLE focus on CD19 as a target. However, his lab is also exploring B cell maturation antigen (BCMA), a marker that is highly expressed on plasma cells. For certain autoimmune diseases, targeting BCMA might be important to deplete pathogenic long-lived plasma cells in the bone marrow, which are not eliminated by CD19-directed therapies.
Dr. Jackson emphasized that although identifying the optimal cell target must be validated in human clinical trials, the next decade promises exciting advances in the treatment of lupus and other humoral autoimmune diseases. Researchers aiming to change the paradigm for these diseases with CAR therapies will need to explore not just different modalities, but also alternative targets like BCMA, he urged.
Ruth Jessen Hickman, MD, a graduate of the Indiana University School of Medicine, is a medical and science writer in Bloomington, Ind.
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