Stem-Cell Gene Therapy for the Wiskott-Aldrich Syndrome

被引：399

作者：

Boztug, Kaan ^{[1
]}

Schmidt, Manfred ^{[3
,4
]}

Schwarzer, Adrian ^{[1
]}

Banerjee, Pinaki P. ^{[6
]}

Diez, Ines Avedillo ^{[1
]}

Dewey, Ricardo A. ^{[1
]}

Boehm, Marie ^{[1
]}

Nowrouzi, Ali ^{[3
,4
]}

Ball, Claudia R. ^{[3
,4
]}

Glimm, Hanno ^{[3
,4
]}

Naundorf, Sonja ^{[5
]}

Kuehlcke, Klaus ^{[5
]}

Blasczyk, Rainer ^{[2
]}

Kondratenko, Irina ^{[7
]}

Marodi, Laszlo ^{[8
]}

Orange, Jordan S. ^{[6
]}

von Kalle, Christof ^{[3
,4
]}

Klein, Christoph ^{[1
]}

机构：

[1] Hannover Med Sch, Dept Pediat Hematol Oncol, D-30625 Hannover, Germany

[2] Hannover Med Sch, Inst Transfus Med, D-30625 Hannover, Germany

[3] Natl Ctr Tumor Dis, Heidelberg, Germany

[4] German Canc Res Ctr, D-6900 Heidelberg, Germany

[5] EUFETS, Idar Oberstein, Germany

[6] Childrens Hosp Philadelphia, Res Inst, Philadelphia, PA 19104 USA

[7] Russian Clin Childrens Hosp, Dept Clin Immunol, Moscow, Russia

[8] Univ Debrecen, Med & Hlth Sci Ctr, Dept Infect & Pediat Immunol, Debrecen, Hungary

来源：

NEW ENGLAND JOURNAL OF MEDICINE | 2010年 / 363卷 / 20期

基金：

美国国家卫生研究院;

关键词：

SEVERE COMBINED IMMUNODEFICIENCY; CHRONIC GRANULOMATOUS-DISEASE; SYNDROME PROTEIN; SCID-X1; WASP; TRANSPLANTATION; HOMEOSTASIS; DEFICIENCY; ACTIVATION; MUTATIONS;

D O I：

10.1056/NEJMoa1003548

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

The Wiskott-Aldrich syndrome (WAS) is an X-linked recessive primary immunodeficiency disorder associated with thrombocytopenia, eczema, and autoimmunity. We treated two patients who had this disorder with a transfusion of autologous, genetically modified hematopoietic stem cells (HSC). We found sustained expression of WAS protein expression in HSC, lymphoid and myeloid cells, and platelets after gene therapy. T and B cells, natural killer (NK) cells, and monocytes were functionally corrected. After treatment, the patients' clinical condition markedly improved, with resolution of hemorrhagic diathesis, eczema, autoimmunity, and predisposition to severe infection. Comprehensive insertion-site analysis showed vector integration that targeted multiple genes controlling growth and immunologic responses in a persistently polyclonal hematopoiesis.

引用

页码：1918 / 1927

页数：10

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