Molecular remission of infant B-ALL after infusion of universal TALEN gene-edited CAR T cells.
Sci Transl Med
; 9(374)2017 01 25.
Article
em En
| MEDLINE
| ID: mdl-28123068
ABSTRACT
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 α 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.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Linfócitos T
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Leucemia-Linfoma Linfoblástico de Células Precursoras B
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Nucleases dos Efetores Semelhantes a Ativadores de Transcrição
Limite:
Female
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Humans
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Infant
Idioma:
En
Ano de publicação:
2017
Tipo de documento:
Article