Mice defective in interferon signaling help distinguish between primary and secondary pathological pathways in a mouse model of neuronal forms of Gaucher disease.
dc.contributor.author | Vardi, Ayelet | |
dc.contributor.author | Ben-Dor, Shifra | |
dc.contributor.author | Cho, Soo Min | |
dc.contributor.author | Kalinke, Ulrich | |
dc.contributor.author | Spanier, Julia | |
dc.contributor.author | Futerman, Anthony H | |
dc.date.accessioned | 2020-09-25T12:00:46Z | |
dc.date.available | 2020-09-25T12:00:46Z | |
dc.date.issued | 2020-09-07 | |
dc.identifier.citation | J Neuroinflammation. 2020 Sep 7;17(1):265. doi: 10.1186/s12974-020-01934-x. | en_US |
dc.identifier.pmid | 32892753 | |
dc.identifier.doi | 10.1186/s12974-020-01934-x | |
dc.identifier.uri | http://hdl.handle.net/10033/622461 | |
dc.description.abstract | Epstein-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.iso | en | en_US |
dc.publisher | BMC | en_US |
dc.rights | Attribution-NonCommercial-ShareAlike 4.0 International | * |
dc.rights.uri | http://creativecommons.org/licenses/by-nc-sa/4.0/ | * |
dc.subject | Gaucher disease | en_US |
dc.subject | Lipid metabolism | en_US |
dc.subject | Lysosomal storage diseases | en_US |
dc.subject | Neurodegenerative diseases | en_US |
dc.subject | Pathogen recognition receptors | en_US |
dc.subject | Type 1 interferon | en_US |
dc.title | Mice 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.type | Article | en_US |
dc.identifier.eissn | 1742-2094 | |
dc.contributor.department | TWINCORE, Zentrum für experimentelle und klinische Infektionsforschung GmbH,Feodor-Lynen Str. 7, 30625 Hannover, Germany. | en_US |
dc.identifier.journal | Journal of neuroinflammation | en_US |
dc.source.volume | 17 | |
dc.source.issue | 1 | |
dc.source.beginpage | 265 | |
dc.source.endpage | ||
refterms.dateFOA | 2020-09-25T12:00:47Z | |
dc.source.journaltitle | Journal of neuroinflammation | |
dc.source.country | England |