Modulating immune responses to AAV by expanded polyclonal T-regs and capsid specific chimeric antigen receptor T-regulatory cells

Immune responses to adeno-associated virus (AAV) capsids limit the therapeutic potential of AAV gene therapy. Herein, we model clinical immune responses by generating AAV capsid-specific chimeric antigen receptor (AAV-CAR) T cells. We then modulate immune responses to AAV capsid with AAV-CAR regulat...

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Autores principales:	Motahareh Arjomandnejad, Katelyn Sylvia, Meghan Blackwood, Thomas Nixon, Qiushi Tang, Manish Muhuri, Alisha M. Gruntman, Guangping Gao, Terence R. Flotte, Allison M. Keeler
Formato:	article
Lenguaje:	EN
Publicado:	Elsevier 2021
Materias:	CAR Tregs AAV gene therapy CAR T regulatory cells chimeric antigen receptor T-regulatory cells immunosuppression immune responses to AAV Genetics QH426-470 Cytology QH573-671
Acceso en línea:	https://doaj.org/article/1d3794b4a1154ad0b895efd390f57d2a
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spelling	oai:doaj.org-article:1d3794b4a1154ad0b895efd390f57d2a2021-11-16T04:10:44ZModulating immune responses to AAV by expanded polyclonal T-regs and capsid specific chimeric antigen receptor T-regulatory cells2329-050110.1016/j.omtm.2021.10.010https://doaj.org/article/1d3794b4a1154ad0b895efd390f57d2a2021-12-01T00:00:00Zhttp://www.sciencedirect.com/science/article/pii/S2329050121001674https://doaj.org/toc/2329-0501Immune responses to adeno-associated virus (AAV) capsids limit the therapeutic potential of AAV gene therapy. Herein, we model clinical immune responses by generating AAV capsid-specific chimeric antigen receptor (AAV-CAR) T cells. We then modulate immune responses to AAV capsid with AAV-CAR regulatory T cells (Tregs). AAV-CAR Tregs in vitro display phenotypical Treg surface marker expression, and functional suppression of effector T cell proliferation and cytotoxicity. In mouse models, AAV-CAR Tregs mediated continued transgene expression from an immunogenic capsid, despite antibody responses, produced immunosuppressive cytokines, and decreased tissue inflammation. AAV-CAR Tregs are also able to bystander suppress immune responses to immunogenic transgenes similarly mediating continued transgene expression, producing immunosuppressive cytokines, and reducing tissue infiltration. Taken together, AAV-CAR T cells and AAV-CAR Tregs are directed and powerful immunosuppressive tools to model and modulate immune responses to AAV capsids and transgenes in the local environment.Motahareh ArjomandnejadKatelyn SylviaMeghan BlackwoodThomas NixonQiushi TangManish MuhuriAlisha M. GruntmanGuangping GaoTerence R. FlotteAllison M. KeelerElsevierarticleCAR TregsAAV gene therapyCAR T regulatory cellschimeric antigen receptor T-regulatory cellsimmunosuppressionimmune responses to AAVGeneticsQH426-470CytologyQH573-671ENMolecular Therapy: Methods & Clinical Development, Vol 23, Iss , Pp 490-506 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	CAR Tregs AAV gene therapy CAR T regulatory cells chimeric antigen receptor T-regulatory cells immunosuppression immune responses to AAV Genetics QH426-470 Cytology QH573-671
spellingShingle	CAR Tregs AAV gene therapy CAR T regulatory cells chimeric antigen receptor T-regulatory cells immunosuppression immune responses to AAV Genetics QH426-470 Cytology QH573-671 Motahareh Arjomandnejad Katelyn Sylvia Meghan Blackwood Thomas Nixon Qiushi Tang Manish Muhuri Alisha M. Gruntman Guangping Gao Terence R. Flotte Allison M. Keeler Modulating immune responses to AAV by expanded polyclonal T-regs and capsid specific chimeric antigen receptor T-regulatory cells
description	Immune responses to adeno-associated virus (AAV) capsids limit the therapeutic potential of AAV gene therapy. Herein, we model clinical immune responses by generating AAV capsid-specific chimeric antigen receptor (AAV-CAR) T cells. We then modulate immune responses to AAV capsid with AAV-CAR regulatory T cells (Tregs). AAV-CAR Tregs in vitro display phenotypical Treg surface marker expression, and functional suppression of effector T cell proliferation and cytotoxicity. In mouse models, AAV-CAR Tregs mediated continued transgene expression from an immunogenic capsid, despite antibody responses, produced immunosuppressive cytokines, and decreased tissue inflammation. AAV-CAR Tregs are also able to bystander suppress immune responses to immunogenic transgenes similarly mediating continued transgene expression, producing immunosuppressive cytokines, and reducing tissue infiltration. Taken together, AAV-CAR T cells and AAV-CAR Tregs are directed and powerful immunosuppressive tools to model and modulate immune responses to AAV capsids and transgenes in the local environment.
format	article
author	Motahareh Arjomandnejad Katelyn Sylvia Meghan Blackwood Thomas Nixon Qiushi Tang Manish Muhuri Alisha M. Gruntman Guangping Gao Terence R. Flotte Allison M. Keeler
author_facet	Motahareh Arjomandnejad Katelyn Sylvia Meghan Blackwood Thomas Nixon Qiushi Tang Manish Muhuri Alisha M. Gruntman Guangping Gao Terence R. Flotte Allison M. Keeler
author_sort	Motahareh Arjomandnejad
title	Modulating immune responses to AAV by expanded polyclonal T-regs and capsid specific chimeric antigen receptor T-regulatory cells
title_short	Modulating immune responses to AAV by expanded polyclonal T-regs and capsid specific chimeric antigen receptor T-regulatory cells
title_full	Modulating immune responses to AAV by expanded polyclonal T-regs and capsid specific chimeric antigen receptor T-regulatory cells
title_fullStr	Modulating immune responses to AAV by expanded polyclonal T-regs and capsid specific chimeric antigen receptor T-regulatory cells
title_full_unstemmed	Modulating immune responses to AAV by expanded polyclonal T-regs and capsid specific chimeric antigen receptor T-regulatory cells
title_sort	modulating immune responses to aav by expanded polyclonal t-regs and capsid specific chimeric antigen receptor t-regulatory cells
publisher	Elsevier
publishDate	2021
url	https://doaj.org/article/1d3794b4a1154ad0b895efd390f57d2a
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Modulating immune responses to AAV by expanded polyclonal T-regs and capsid specific chimeric antigen receptor T-regulatory cells

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