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

Christoph T. Ellebrecht, Vijay G. 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 S. Payne

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish
Pages (from-to)179-184
Number of pages6
JournalScience
Volume353
Issue number6295
DOIs
Publication statusPublished - Jul 8 2016

ASJC Scopus subject areas

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    Ellebrecht, C. T., Bhoj, V. G., Nace, A., Choi, E. J., Mao, X., Cho, M. J., Di Zenzo, G., Lanzavecchia, A., Seykora, J. T., Cotsarelis, G., Milone, M. C., & Payne, A. S. (2016). Reengineering chimeric antigen receptor T cells for targeted therapy of autoimmune disease. Science, 353(6295), 179-184. https://doi.org/10.1126/science.aaf6756