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

@article{Qasim2017MolecularRO,
  title={Molecular remission of infant B-ALL after infusion of universal TALEN gene-edited CAR T cells},
  author={Waseem Qasim and Hong Zhan and Sujith Samarasinghe and Stuart P Adams and Persis J Amrolia and Sian Stafford and Katie Butler and Christine Rivat and Gary Wright and Kathy Somana and Sara Ghorashian and Danielle Pinner and Gulrukh Ahsan and Kimberly C. Gilmour and Giovanna Lucchini and Sarah Inglott and William Mifsud and Robert Chiesa and Karl S. Peggs and Lucas Chan and Farzin Farzaneh and Adrian James Thrasher and Ajay Vora and Martin A. Pule and Paul A. Veys},
  journal={Science Translational Medicine},
  year={2017},
  volume={9}
}
  • W. Qasim, H. Zhan, P. Veys
  • Published 25 January 2017
  • Medicine, Biology
  • Science Translational Medicine
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. [] Key Method 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…
Double TALEN-edited T-cells kick B-ALL into touch
TLDR
A positive step in the direction of universal CAR cells is reported in two paediatric patients with refractory-relapsed B-ALL using TALEN-edited allogeneic CAR19 T cells, which highlights the challenges and complexities of gene engineering, bordering on the field of synthetic biology.
Successful translation and future prospects of TALEN editing for leukemia patients
TLDR
There has been marked interest in generating an ‘off-the-shelf’, universal CAR T cell that could be derived from unrelated donors, because these are patient-specific therapies that have proven to be expensive, time-consuming, and in some cases technically difficult.
Sleeping Beauty-engineered CAR T cells achieve anti-leukemic activity without severe toxicities.
TLDR
SB-engineered CAR T cells expand and persist in pediatric and adult B-ALL patients relapsed after HSCT, and anti-leukemic activity was achieved without severe toxicities.
Posttransplant chimeric antigen receptor therapy.
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Different approaches to mitigate the risk of causing or aggravating graft-versus-host disease (GVHD) are reviewed, including CAR therapies based on donor leukocyte infusion, virus-specific T cells, T-cell receptor-deficient T cell, lymphoid progenitor cells, and regulatory T cells.
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TLDR
This review will summarize the published data thus far on the use of CAR-modified T-cell therapy in pediatric B-ALL and outline the various CAR products now being developed for this population.
Allogeneic CAR-T Cells: More than Ease of Access?
TLDR
Healthy donor, gene-edited CAR-T cells which do not require human leucocyte antigen (HLA) matching have the potential to provide an ‘off the shelf’ product, overcoming the manufacturing difficulties of producing CAR- T cells for each individual patient.
Preclinical Evaluation of Allogeneic CAR T Cells Targeting BCMA for the Treatment of Multiple Myeloma.
Donor T cells for CAR T cell therapy
TLDR
Donor T cells provide a good source of immune cells for adoptive immunotherapy and can be used to generate universal off-the-shelf CAR T cells that are readily available for administration into patients as required.
Hematopoietic Stem Cell Transplantation in the Era of Engineered Cell Therapy
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There are early signals that subsequent transplantation of patients who have achieved remission with CAR-T may be a potentially viable (though expensive) strategy.
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