Reengineering chimeric antigen receptor T cells for targeted therapy of autoimmune disease

作者：Christoph T. Ellebrecht, Vijay Bhoj, Arben Nace, Eun Jung Choi, Xuming Mao, Michael Jeffrey Cho, Giovanni Di Zenzo, Antonio Lanzavecchia, John T. Seykora, George Cotsarelis, Michael C. Milone, Aimee Payne · 发表于：Science · 年份：2016 · DOI：10.1126/science.aaf6756 · 被引用次数：729 · 研究领域：CAR-T cell therapy research、Nanofabrication and Lithography Techniques、Transgenic Plants and Applications

Ideally, therapy for autoimmune diseases should eliminate pathogenic autoimmune cells while sparing protective immunity, but feasible strategies for such an approach have been elusive. Here, we show that in the antibody-mediated autoimmune disease pemphigus vulgaris (PV), autoantigen-based chimeric immunoreceptors can direct T cells to kill autoreactive B lymphocytes through the specificity of the B cell receptor (BCR). We engineered human T cells to express a chimeric autoantibody receptor (CAAR), consisting of the PV autoantigen, desmoglein (Dsg) 3, fused to CD137-CD3ζ signaling domains. Dsg3 CAAR-T cells exhibit specific cytotoxicity against cells expressing anti-Dsg3 BCRs in vitro and expand, persist, and specifically eliminate Dsg3-specific B cells in vivo. CAAR-T cells may provide an effective and universal strategy for specific targeting of autoreactive B cells in antibody-mediated autoimmune disease.