Mice defective in interferon signaling help distinguish between primary and secondary pathological pathways in a mouse model of neuronal forms of Gaucher disease.
Cast your vote
You can rate an item by clicking the amount of stars they wish to award to this item.
When enough users have cast their vote on this item, the average rating will also be shown.
Your vote was cast
Thank you for your feedback
Thank you for your feedback
MetadataShow full item record
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.
CitationJ Neuroinflammation. 2020 Sep 7;17(1):265. doi: 10.1186/s12974-020-01934-x.
AffiliationTWINCORE, Zentrum für experimentelle und klinische Infektionsforschung GmbH,Feodor-Lynen Str. 7, 30625 Hannover, Germany.
JournalJournal of neuroinflammation
The following license files are associated with this item:
- Creative Commons
Except where otherwise noted, this item's license is described as Attribution-NonCommercial-ShareAlike 4.0 International
- Substrate reduction therapy using Genz-667161 reduces levels of pathogenic components in a mouse model of neuronopathic forms of Gaucher disease.
- Authors: Blumenreich S, Yaacobi C, Vardi A, Barav OB, Vitner EB, Park H, Wang B, Cheng SH, Sardi SP, Futerman AH
- Issue date: 2020 Aug 3
- Induction of the type I interferon response in neurological forms of Gaucher disease.
- Authors: Vitner EB, Farfel-Becker T, Ferreira NS, Leshkowitz D, Sharma P, Lang KS, Futerman AH
- Issue date: 2016 May 12
- Multiple pathogenic proteins implicated in neuronopathic Gaucher disease mice.
- Authors: Xu YH, Xu K, Sun Y, Liou B, Quinn B, Li RH, Xue L, Zhang W, Setchell KD, Witte D, Grabowski GA
- Issue date: 2014 Aug 1
- Delineating pathological pathways in a chemically induced mouse model of Gaucher disease.
- Authors: Vardi A, Zigdon H, Meshcheriakova A, Klein AD, Yaacobi C, Eilam R, Kenwood BM, Rahim AA, Massaro G, Merrill AH Jr, Vitner EB, Futerman AH
- Issue date: 2016 Aug
- Modulating ryanodine receptors with dantrolene attenuates neuronopathic phenotype in Gaucher disease mice.
- Authors: Liou B, Peng Y, Li R, Inskeep V, Zhang W, Quinn B, Dasgupta N, Blackwood R, Setchell KD, Fleming S, Grabowski GA, Marshall J, Sun Y
- Issue date: 2016 Dec 1