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Science. 2016 Jul 8;353(6295):179-84. doi: 10.1126/science.aaf6756. Epub 2016 Jun 30.

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

Author information

1
Department of Dermatology, University of Pennsylvania, Philadelphia, PA 19104, USA.
2
Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
3
Laboratory of Molecular and Cellular Biology, Istituto Dermopatico dell'Immacolata (IDI-IRCCS), 00167 Rome, Italy.
4
Institute for Research in Biomedicine, 6500 Bellinzona, Switzerland.
5
Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA. aimee.payne@uphs.upenn.edu milone@mail.med.upenn.edu.
6
Department of Dermatology, University of Pennsylvania, Philadelphia, PA 19104, USA. aimee.payne@uphs.upenn.edu milone@mail.med.upenn.edu.

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.

PMID:
27365313
PMCID:
PMC5343513
DOI:
10.1126/science.aaf6756
[Indexed for MEDLINE]
Free PMC Article

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