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Genome edited allogeneic donor 'universal' chimeric antigen receptor T Cells

Qasim, Waseem; (2023) Genome edited allogeneic donor 'universal' chimeric antigen receptor T Cells. Blood , 141 (8) pp. 835-845. 10.1182/blood.2022016204. Green open access

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Abstract

αβ T cell receptor (TCRαβ) T cells modified to express chimeric antigen receptors (CAR), are now available as authorized therapies for certain B-cell malignancies. However the process of autologous harvest and generation of patient-specific products is costly, with complex logistics and infrastructure requirements. Premanufactured banks of allogeneic donor–derived CAR T cells could help widen applicability if the challenges of HLA-mismatched T-cell therapy can be addressed. Genome editing is being applied to overcome allogeneic barriers, most notably, by disrupting TCRαβ to prevent graft-versus-host disease, and multiple competing editing technologies, including CRISPR/Cas9 and base editing, have reached clinical phase testing. Improvements in accuracy and efficiency have unlocked applications for a wider range of blood malignancies, with multiplexed editing incorporated to target HLA molecules, shared antigens and checkpoint pathways. Clinical trials will help establish safety profiles and determine the durability of responses as well as the role of consolidation with allogeneic transplantation.

Type: Article
Title: Genome edited allogeneic donor 'universal' chimeric antigen receptor T Cells
Location: United States
Open access status: An open access version is available from UCL Discovery
DOI: 10.1182/blood.2022016204
Publisher version: https://doi.org/10.1182/blood.2022016204
Language: English
Additional information: Copyright © 2023 by The American Society of Hematology. Licensed under Creative Commons AttributionNonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved. See: https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode
Keywords: Free Research Articles, Gene Therapy, Immunobiology and Immunotherapy, Review Articles, Review Series, Transplantation
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health > Infection, Immunity and Inflammation Dept
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
URI: https://discovery.ucl.ac.uk/id/eprint/10158238
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