An inducible caspase 9 safety switch can halt cell therapy-induced autoimmune disease

被引：27

作者：

de Witte, Moniek A. ^{[1
]}

Jorritsma, Annelies ^{[1
]}

Swart, Erwin ^{[1
]}

Straathof, Karin C. ^{[3
]}

de Punder, Karin ^{[2
]}

Haanen, John B. A. G. ^{[1
]}

Rooney, Cliona M. ^{[3
]}

Schumacher, Ton N. M. ^{[1
]}

机构：

[1] Netherlands Canc Inst, Div Immunol, NL-1066 CX Amsterdam, Netherlands

[2] Netherlands Canc Inst, Div Expt Anim Pathol, NL-1066 CX Amsterdam, Netherlands

[3] Baylor Coll Med, Ctr Cell & Gene Therapy, Houston, TX 77030 USA

来源：

JOURNAL OF IMMUNOLOGY | 2008年 / 180卷 / 09期

关键词：

D O I：

10.4049/jimmunol.180.9.6365

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

Transfer of either allogeneic or genetically modified T cells as a therapy for malignancies can be accompanied by T cell-mediated tissue destruction. The introduction of an efficient "safety switch" can potentially be used to control the survival of adoptively transferred cell populations and as such reduce the risk of severe graft-vs-host disease. In this study, we have tested the value of an inducible caspase 9-based safety switch to halt an ongoing immune attack in a murine model for cell therapy-induced type I diabetes. The data obtained in this model indicate that self-reactive T cells expressing this conditional safety switch show unimpaired lymphopenia- and vaccine-induced proliferation and effector function in vivo, but can be specifically and rapidly eliminated upon triggering. These data provide strong support for the evaluation of this conditional safety switch in clinical trials of adoptive cell therapy.

引用

页码：6365 / 6373

页数：9

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