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dc.contributor.authorGernoux, Gwladys
dc.contributor.authorWilson, James M.
dc.contributor.authorMueller, Christian
dc.date2022-08-11T08:08:21.000
dc.date.accessioned2022-08-23T15:52:07Z
dc.date.available2022-08-23T15:52:07Z
dc.date.issued2017-04-01
dc.date.submitted2017-06-02
dc.identifier.citationHum Gene Ther. 2017 Apr;28(4):338-349. doi: 10.1089/hum.2017.022. <a href="https://doi.org/10.1089/hum.2017.022">Link to article on publisher's site</a>
dc.identifier.issn1043-0342 (Linking)
dc.identifier.doi10.1089/hum.2017.022
dc.identifier.pmid28323492
dc.identifier.urihttp://hdl.handle.net/20.500.14038/29069
dc.description.abstractRecombinant adeno-associated viruses (AAVs) are quickly becoming the preferred viral vector for viral gene delivery for the treatment of a wide variety of genetic disorders. However, since their use in a clinical trial targeting hemophilia B patients 10 years ago, immune responses to the AAV capsid appear to have hampered some of the early clinical gene transfer efficacy. Indeed, AAV-based gene transfer has been shown to reactivate capsid-specific memory T cells, which have correlated with a decline in AAV-transduced tissue in some patients. Importantly, clinical trials have also shown that this reactivation can be quelled by administering time-course taper of glucocorticoid steroids before or after dosing. More recently, two clinical studies have shown that AAV gene transfer is not only able to induce a deleterious immune response, but also can result in the initiation of a tolerance to the AAV capsid mediated by regulatory T cells and exhausted T cells. This article reviews clinical trials describing immune responses to AAV, as well as the mechanisms responsible for immune tolerance in chronic infections and how it could apply to AAV-based gene transfer. A better understanding of both cytotoxic and tolerogenic immune responses to recombinant AAV will lead to safer gene transfer protocols in patients.
dc.language.isoen_US
dc.relation<a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&list_uids=28323492&dopt=Abstract">Link to Article in PubMed</a>
dc.relation.urlhttps://doi.org/10.1089/hum.2017.022
dc.subjectAAV
dc.subjectCTL
dc.subjectT cell exhaustion
dc.subjectTreg
dc.subjectimmune response
dc.subjectregulatory T cell
dc.subjectGenetics and Genomics
dc.subjectImmunity
dc.subjectImmunoprophylaxis and Therapy
dc.subjectTherapeutics
dc.titleRegulatory and Exhausted T Cell Responses to AAV Capsid
dc.typeJournal Article
dc.source.journaltitleHuman gene therapy
dc.source.volume28
dc.source.issue4
dc.identifier.legacycoverpagehttps://escholarship.umassmed.edu/faculty_pubs/1297
dc.identifier.contextkey10243086
html.description.abstract<p>Recombinant adeno-associated viruses (AAVs) are quickly becoming the preferred viral vector for viral gene delivery for the treatment of a wide variety of genetic disorders. However, since their use in a clinical trial targeting hemophilia B patients 10 years ago, immune responses to the AAV capsid appear to have hampered some of the early clinical gene transfer efficacy. Indeed, AAV-based gene transfer has been shown to reactivate capsid-specific memory T cells, which have correlated with a decline in AAV-transduced tissue in some patients. Importantly, clinical trials have also shown that this reactivation can be quelled by administering time-course taper of glucocorticoid steroids before or after dosing. More recently, two clinical studies have shown that AAV gene transfer is not only able to induce a deleterious immune response, but also can result in the initiation of a tolerance to the AAV capsid mediated by regulatory T cells and exhausted T cells. This article reviews clinical trials describing immune responses to AAV, as well as the mechanisms responsible for immune tolerance in chronic infections and how it could apply to AAV-based gene transfer. A better understanding of both cytotoxic and tolerogenic immune responses to recombinant AAV will lead to safer gene transfer protocols in patients.</p>
dc.identifier.submissionpathfaculty_pubs/1297
dc.contributor.departmentDepartment of Pediatrics, Division of Pediatric Pulmonology
dc.contributor.departmentGene Therapy Center
dc.source.pages338-349


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