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dc.contributor.authorVardi, Ayelet
dc.contributor.authorBen-Dor, Shifra
dc.contributor.authorCho, Soo Min
dc.contributor.authorKalinke, Ulrich
dc.contributor.authorSpanier, Julia
dc.contributor.authorFuterman, Anthony H
dc.date.accessioned2020-09-25T12:00:46Z
dc.date.available2020-09-25T12:00:46Z
dc.date.issued2020-09-07
dc.identifier.citationJ Neuroinflammation. 2020 Sep 7;17(1):265. doi: 10.1186/s12974-020-01934-x.en_US
dc.identifier.pmid32892753
dc.identifier.doi10.1186/s12974-020-01934-x
dc.identifier.urihttp://hdl.handle.net/10033/622461
dc.description.abstractEpstein-Barr virus (EBV) is a latent and oncogenic human herpesvirus. Lytic viral protein expression plays an important role in EBV-associated malignancies. The EBV envelope glycoprotein 350 (gp350) is expressed abundantly during EBV lytic reactivation and sporadically on the surface of latently infected cells. Here we tested T cells expressing gp350-specific chimeric antigen receptors (CARs) containing scFvs derived from two novel gp350-binding, highly neutralizing monoclonal antibodies. The scFvs were fused to CD28/CD3ζ signaling domains in a retroviral vector. The produced gp350CAR-T cells specifically recognized and killed gp350+ 293T cells in vitro. The best-performing 7A1-gp350CAR-T cells were cytotoxic against the EBV+ B95-8 cell line, showing selectivity against gp350+ cells. Fully humanized Nod.Rag.Gamma mice transplanted with cord blood CD34+ cells and infected with the EBV/M81/fLuc lytic strain were monitored dynamically for viral spread. Infected mice recapitulated EBV-induced lymphoproliferation, tumor development, and systemic inflammation. We tested adoptive transfer of autologous CD8+gp350CAR-T cells administered protectively or therapeutically. After gp350CAR-T cell therapy, 75% of mice controlled or reduced EBV spread and showed lower frequencies of EBER+ B cell malignant lymphoproliferation, lack of tumor development, and reduced inflammation. In summary, CD8+gp350CAR-T cells showed proof-of-concept preclinical efficacy against impending EBV+ lymphoproliferation and lymphomagenesis.en_US
dc.language.isoenen_US
dc.publisherBMCen_US
dc.rightsAttribution-NonCommercial-ShareAlike 4.0 International*
dc.rights.urihttp://creativecommons.org/licenses/by-nc-sa/4.0/*
dc.subjectGaucher diseaseen_US
dc.subjectLipid metabolismen_US
dc.subjectLysosomal storage diseasesen_US
dc.subjectNeurodegenerative diseasesen_US
dc.subjectPathogen recognition receptorsen_US
dc.subjectType 1 interferonen_US
dc.titleMice defective in interferon signaling help distinguish between primary and secondary pathological pathways in a mouse model of neuronal forms of Gaucher disease.en_US
dc.typeArticleen_US
dc.identifier.eissn1742-2094
dc.contributor.departmentTWINCORE, Zentrum für experimentelle und klinische Infektionsforschung GmbH,Feodor-Lynen Str. 7, 30625 Hannover, Germany.en_US
dc.identifier.journalJournal of neuroinflammationen_US
dc.source.volume17
dc.source.issue1
dc.source.beginpage265
dc.source.endpage
refterms.dateFOA2020-09-25T12:00:47Z
dc.source.journaltitleJournal of neuroinflammation
dc.source.countryEngland


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