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

115 Citations (Scopus)

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

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Antigen Receptors
Cell- and Tissue-Based Therapy
Autoimmune Diseases
B-Lymphocytes
Autoantibodies
Pemphigus
Autoantigens
T-Cell Antigen Receptor
Desmoglein 3
T-Lymphocytes
Antibodies
Immunity
Therapeutics

ASJC Scopus subject areas

  • General

Cite this

Ellebrecht, C. T., Bhoj, V. G., Nace, A., Choi, E. J., Mao, X., Cho, M. J., ... 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

Reengineering chimeric antigen receptor T cells for targeted therapy of autoimmune disease. / Ellebrecht, Christoph T.; Bhoj, Vijay G.; Nace, Arben; Choi, Eun Jung; Mao, Xuming; Cho, Michael Jeffrey; Di Zenzo, Giovanni; Lanzavecchia, Antonio; Seykora, John T.; Cotsarelis, George; Milone, Michael C.; Payne, Aimee S.

In: Science, Vol. 353, No. 6295, 08.07.2016, p. 179-184.

Research output: Contribution to journalArticle

Ellebrecht, CT, Bhoj, VG, Nace, A, Choi, EJ, Mao, X, Cho, MJ, Di Zenzo, G, Lanzavecchia, A, Seykora, JT, Cotsarelis, G, Milone, MC & Payne, AS 2016, 'Reengineering chimeric antigen receptor T cells for targeted therapy of autoimmune disease', Science, vol. 353, no. 6295, pp. 179-184. https://doi.org/10.1126/science.aaf6756
Ellebrecht CT, Bhoj VG, Nace A, Choi EJ, Mao X, Cho MJ et al. Reengineering chimeric antigen receptor T cells for targeted therapy of autoimmune disease. Science. 2016 Jul 8;353(6295):179-184. https://doi.org/10.1126/science.aaf6756
Ellebrecht, Christoph T. ; Bhoj, Vijay G. ; Nace, Arben ; Choi, Eun Jung ; Mao, Xuming ; Cho, Michael Jeffrey ; Di Zenzo, Giovanni ; Lanzavecchia, Antonio ; Seykora, John T. ; Cotsarelis, George ; Milone, Michael C. ; Payne, Aimee S. / Reengineering chimeric antigen receptor T cells for targeted therapy of autoimmune disease. In: Science. 2016 ; Vol. 353, No. 6295. pp. 179-184.
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