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

W Qasim, H Zhan, S Samarasinghe, S Adams… - Science translational …, 2017 - science.org
W Qasim, H Zhan, S Samarasinghe, S Adams, P Amrolia, S Stafford, K Butler, C Rivat…
Science translational medicine, 2017science.org
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 …
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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