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

被引：534

作者：

Ellebrecht, Christoph T. ^{[1
]}

Bhoj, Vijay G. ^{[2
]}

Nace, Arben ^{[1
]}

Choi, Eun Jung ^{[1
]}

Mao, Xuming ^{[1
]}

Cho, Michael Jeffrey ^{[1
]}

Di Zenzo, Giovanni ^{[3
]}

Lanzavecchia, Antonio ^{[4
]}

Seykora, John T. ^{[1
]}

Cotsarelis, George ^{[1
]}

Milone, Michael C. ^{[2
]}

Payne, Aimee S. ^{[1
]}

机构：

[1] Univ Penn, Dept Dermatol, Philadelphia, PA 19104 USA

[2] Univ Penn, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA

[3] IDI IRCCS, Mol & Cellular Biol Lab, I-00167 Rome, Italy

[4] Inst Biomed Res, CH-6500 Bellinzona, Switzerland

来源：

SCIENCE | 2016年 / 353卷 / 6295期

关键词：

B-CELL; PEMPHIGUS-VULGARIS; PERSISTENCE; ACTIVATION; 4-1BB; DESMOGLEIN-3; MALIGNANCIES; SEGREGATION; INTERFACE; LYMPHOMA;

D O I：

10.1126/science.aaf6756

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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-CD3 zeta 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.

引用

页码：179 / 184

页数：6

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