Chimeric antigen receptors and regulatory T cells: the potential for HLA-specific immunosuppression in transplantation

Chimeric antigen receptors (CARs) are a breakthrough in genetic engineering that have revolutionized the field of adoptive cellular therapy (ACT). Cells expressing these receptors are rerouted to a predefined target by the inclusion of an antigen-specific binding region within the synthetic CAR cons...

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Main Authors: Wright, S, Hennessy, C, Hester, J, Issa, F
Format: Journal article
Language:English
Published: Elsevier 2021
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author Wright, S
Hennessy, C
Hester, J
Issa, F
author_facet Wright, S
Hennessy, C
Hester, J
Issa, F
author_sort Wright, S
collection OXFORD
description Chimeric antigen receptors (CARs) are a breakthrough in genetic engineering that have revolutionized the field of adoptive cellular therapy (ACT). Cells expressing these receptors are rerouted to a predefined target by the inclusion of an antigen-specific binding region within the synthetic CAR construct. The advantage of cells with programmed specificity has been demonstrated clinically in the field of oncology, and it is clear that such cells have greater accuracy, potency, and reduced off-target therapeutic effects compared with their unmodified counterparts. In contrast to conventional T cells (Tconvs), regulatory T cells (Tregs) play a major role in suppressing immune activation and regulating the host immune response. CAR expression within Tregs has been proposed as a therapy for autoimmune and inflammatory diseases, graft-versus-host disease (GVHD), and organ transplant rejection. In the latter, they hold immense potential as mediators of immune tolerance for recipients of allotransplants. However, current research into CAR-Treg engineering is extremely limited, and there is uncertainty regarding optimal design for therapeutic use. This review examines the rationale behind the development of CAR-Tregs, their significance for human transplantation, potential designs, safety considerations, and comparisons of CAR-Tregs in transplantation models to date.
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spelling oxford-uuid:15006325-8f59-43ef-8b08-f4cfab87594b2022-11-01T10:42:21ZChimeric antigen receptors and regulatory T cells: the potential for HLA-specific immunosuppression in transplantationJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:15006325-8f59-43ef-8b08-f4cfab87594bEnglishSymplectic ElementsElsevier2021Wright, SHennessy, CHester, JIssa, FChimeric antigen receptors (CARs) are a breakthrough in genetic engineering that have revolutionized the field of adoptive cellular therapy (ACT). Cells expressing these receptors are rerouted to a predefined target by the inclusion of an antigen-specific binding region within the synthetic CAR construct. The advantage of cells with programmed specificity has been demonstrated clinically in the field of oncology, and it is clear that such cells have greater accuracy, potency, and reduced off-target therapeutic effects compared with their unmodified counterparts. In contrast to conventional T cells (Tconvs), regulatory T cells (Tregs) play a major role in suppressing immune activation and regulating the host immune response. CAR expression within Tregs has been proposed as a therapy for autoimmune and inflammatory diseases, graft-versus-host disease (GVHD), and organ transplant rejection. In the latter, they hold immense potential as mediators of immune tolerance for recipients of allotransplants. However, current research into CAR-Treg engineering is extremely limited, and there is uncertainty regarding optimal design for therapeutic use. This review examines the rationale behind the development of CAR-Tregs, their significance for human transplantation, potential designs, safety considerations, and comparisons of CAR-Tregs in transplantation models to date.
spellingShingle Wright, S
Hennessy, C
Hester, J
Issa, F
Chimeric antigen receptors and regulatory T cells: the potential for HLA-specific immunosuppression in transplantation
title Chimeric antigen receptors and regulatory T cells: the potential for HLA-specific immunosuppression in transplantation
title_full Chimeric antigen receptors and regulatory T cells: the potential for HLA-specific immunosuppression in transplantation
title_fullStr Chimeric antigen receptors and regulatory T cells: the potential for HLA-specific immunosuppression in transplantation
title_full_unstemmed Chimeric antigen receptors and regulatory T cells: the potential for HLA-specific immunosuppression in transplantation
title_short Chimeric antigen receptors and regulatory T cells: the potential for HLA-specific immunosuppression in transplantation
title_sort chimeric antigen receptors and regulatory t cells the potential for hla specific immunosuppression in transplantation
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AT hennessyc chimericantigenreceptorsandregulatorytcellsthepotentialforhlaspecificimmunosuppressionintransplantation
AT hesterj chimericantigenreceptorsandregulatorytcellsthepotentialforhlaspecificimmunosuppressionintransplantation
AT issaf chimericantigenreceptorsandregulatorytcellsthepotentialforhlaspecificimmunosuppressionintransplantation