Qasim, W;
Zhan, H;
Samarasinghe, S;
Adams, S;
Amrolia, P;
Stafford, S;
Butler, K;
... Veys, P; + view all
(2017)
Molecular remission of infant B-ALL after infusion of universal TALEN gene-edited CAR T cells.
Science Translational Medicine
, 9
(374)
, Article eaaj2013. 10.1126/scitranslmed.aaj2013.
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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.
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