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Sci Transl Med. 2017 Jan 25;9(374). pii: eaaj2013. doi: 10.1126/scitranslmed.aaj2013.

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

Author information

1
Great Ormond Street Institute of Child Health, University College London, London WC1N 1EH, UK. w.qasim@ucl.ac.uk.
2
Great Ormond Street Hospital National Health Service Trust, London WC1N 1LE, UK.
3
Great Ormond Street Institute of Child Health, University College London, London WC1N 1EH, UK.
4
Cancer Institute, University College London, London WC1E 6DD, UK.
5
Division of Cancer Studies, Department of Haematological Medicine, King's College London, London SE5 9NU, UK.
6
Sheffield Children's Hospital, Sheffield S10 2TH, UK.

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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PMID:
28123068
DOI:
10.1126/scitranslmed.aaj2013
[Indexed for MEDLINE]

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