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dc.contributor.authorArjomandnejad, Motahareh
dc.contributor.authorSylvia, Katelyn
dc.contributor.authorBlackwood, Meghan
dc.contributor.authorNixon, Thomas
dc.contributor.authorTang, Qiushi
dc.contributor.authorMuhuri, Manish
dc.contributor.authorGruntman, Alisha M
dc.contributor.authorGao, Guangping
dc.contributor.authorFlotte, Terence R
dc.contributor.authorKeeler, Allison M
dc.date.accessioned2023-02-09T20:46:14Z
dc.date.available2023-02-09T20:46:14Z
dc.date.issued2021-10-28
dc.identifier.citationArjomandnejad M, Sylvia K, Blackwood M, Nixon T, Tang Q, Muhuri M, Gruntman AM, Gao G, Flotte TR, Keeler AM. Modulating immune responses to AAV by expanded polyclonal T-regs and capsid specific chimeric antigen receptor T-regulatory cells. Mol Ther Methods Clin Dev. 2021 Oct 28;23:490-506. doi: 10.1016/j.omtm.2021.10.010. PMID: 34853797; PMCID: PMC8605179.en_US
dc.identifier.issn2329-0501
dc.identifier.doi10.1016/j.omtm.2021.10.010en_US
dc.identifier.pmid34853797
dc.identifier.urihttp://hdl.handle.net/20.500.14038/51667
dc.description.abstractImmune 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.en_US
dc.language.isoenen_US
dc.relation.ispartofMolecular Therapy – Methods & Clinical Developmenten_US
dc.relation.urlhttps://doi.org/10.1016/j.omtm.2021.10.010en_US
dc.rightsCopyright 2021 The Author(s). This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).en_US
dc.rightsAttribution-NonCommercial-NoDerivatives 4.0 International*
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/*
dc.subjectAAV gene therapyen_US
dc.subjectCAR T regulatory cellsen_US
dc.subjectCAR Tregsen_US
dc.subjectchimeric antigen receptor T-regulatory cellsen_US
dc.subjectimmune responses to AAVen_US
dc.subjectimmune responses to capsiden_US
dc.subjectimmune responses to transgeneen_US
dc.subjectimmunosuppressionen_US
dc.titleModulating immune responses to AAV by expanded polyclonal T-regs and capsid specific chimeric antigen receptor T-regulatory cellsen_US
dc.typeJournal Articleen_US
dc.source.journaltitleMolecular therapy. Methods & clinical development
dc.source.volume23
dc.source.beginpage490
dc.source.endpage506
dc.source.countryUnited States
dc.source.countryUnited States
dc.source.countryUnited States
dc.identifier.journalMolecular therapy. Methods & clinical development
refterms.dateFOA2023-02-09T20:46:15Z
dc.contributor.departmentHorae Gene Therapy Centeren_US
dc.contributor.departmentMicrobiology and Physiological Systemsen_US
dc.contributor.departmentNeuroNexus Instituteen_US
dc.contributor.departmentPediatricsen_US


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Copyright 2021 The Author(s).
This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
Except where otherwise noted, this item's license is described as Copyright 2021 The Author(s). This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).