Molecular remission of infant B-ALL after infusion of universal TALEN gene-edited CAR T cells

被引：719

作者：

Qasim, Waseem ^{[1
,2
]}

Zhan, Hong ^{[1
]}

Samarasinghe, Sujith ^{[2
]}

Adams, Stuart ^{[2
]}

Amrolia, Persis ^{[1
,2
]}

Stafford, Sian ^{[1
]}

Butler, Katie ^{[1
]}

Rivat, Christine ^{[1
]}

Wright, Gary ^{[2
]}

Somana, Kathy ^{[2
]}

Ghorashian, Sara ^{[1
]}

Pinner, Danielle ^{[2
]}

Ahsan, Gul ^{[2
]}

Gilmour, Kimberly ^{[2
]}

Lucchini, Giovanna ^{[2
]}

Inglott, Sarah ^{[2
]}

Mifsud, William ^{[2
]}

Chiesa, Robert ^{[2
]}

Peggs, Karl S. ^{[3
]}

Chan, Lucas ^{[4
]}

Farzaneh, Farzin ^{[4
]}

Thrasher, Adrian J. ^{[1
]}

Vora, Ajay ^{[5
]}

Pule, Martin ^{[3
]}

Veys, Paul ^{[1
]}

机构：

[1] UCL, Great Ormond St Inst Child Hlth, London WC1N 1EH, England

[2] Great Ormond St Hosp Natl Hlth Serv Trust, London WC1N 1LE, England

[3] UCL, Canc Inst, London WC1E 6DD, England

[4] Kings Coll London, Dept Haematol Med, Div Canc Studies, London SE5 9NU, England

[5] Sheffield Childrens Hosp, Sheffield S10 2TH, S Yorkshire, England

来源：

SCIENCE TRANSLATIONAL MEDICINE | 2017年 / 9卷 / 374期

基金：

英国生物技术与生命科学研究理事会; 美国国家卫生研究院; 英国惠康基金;

关键词：

TRANSPLANTATION; CD19; IMMUNITY;

D O I：

10.1126/scitranslmed.aaj2013

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Autologous T cells engineered to express chimeric antigen receptor against the B cell antigen CD19 (CAR19) are achieving marked leukemic remissions in early-phase trials but can be difficult to manufacture, especially in infants or heavily treated patients. We generated universal CAR19 (UCART19) T cells by lentiviral transduction of non-human leukocyte antigen-matched donor cells and simultaneous transcription activator-like effector nuclease (TALEN)-mediated gene editing of T cell receptor a chain and CD52 gene loci. Two infants with relapsed refractory CD19(+) B cell acute lymphoblastic leukemia received lymphodepleting chemotherapy and anti-CD52 serotherapy, followed by a single-dose infusion of UCART19 cells. Molecular remissions were achieved within 28 days in both infants, and UCART19 cells persisted until conditioning ahead of successful allogeneic stem cell transplantation. This bridge-to-transplantation strategy demonstrates the therapeutic potential of gene-editing technology.

引用

页数：8

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