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Open Access 01-12-2012 | Research

CAR/FoxP3-engineered T regulatory cells target the CNS and suppress EAE upon intranasal delivery

Authors: Moa Fransson, Elena Piras, Joachim Burman, Berith Nilsson, Magnus Essand, BinFeng Lu, Robert A Harris, Peetra U Magnusson, Eva Brittebo, Angelica SI Loskog

Published in: Journal of Neuroinflammation | Issue 1/2012

Abstract

Background

Multiple sclerosis (MS) is an autoimmune disease of the central nervous system (CNS). In the murine experimental autoimmune encephalomyelitis (EAE) model of MS, T regulatory (Treg) cell therapy has proved to be beneficial, but generation of stable CNS-targeting Tregs needs further development. Here, we propose gene engineering to achieve CNS-targeting Tregs from naïve CD4 cells and demonstrate their efficacy in the EAE model.

Methods

CD4⁺ T cells were modified utilizing a lentiviral vector system to express a chimeric antigen receptor (CAR) targeting myelin oligodendrocyte glycoprotein (MOG) in trans with the murine FoxP3 gene that drives Treg differentiation. The cells were evaluated in vitro for suppressive capacity and in C57BL/6 mice to treat EAE. Cells were administered by intranasal (i.n.) cell delivery.

Results

The engineered Tregs demonstrated suppressive capacity in vitro and could efficiently access various regions in the brain via i.n cell delivery. Clinical score 3 EAE mice were treated and the engineered Tregs suppressed ongoing encephalomyelitis as demonstrated by reduced disease symptoms as well as decreased IL-12 and IFNgamma mRNAs in brain tissue. Immunohistochemical markers for myelination (MBP) and reactive astrogliosis (GFAP) confirmed recovery in mice treated with engineered Tregs compared to controls. Symptom-free mice were rechallenged with a second EAE-inducing inoculum but remained healthy, demonstrating the sustained effect of engineered Tregs.

Conclusion

CNS-targeting Tregs delivered i.n. localized to the CNS and efficiently suppressed ongoing inflammation leading to diminished disease symptoms.

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Title: CAR/FoxP3-engineered T regulatory cells target the CNS and suppress EAE upon intranasal delivery
Authors: Moa Fransson
Elena Piras
Joachim Burman
Berith Nilsson
Magnus Essand
BinFeng Lu
Robert A Harris
Peetra U Magnusson
Eva Brittebo
Angelica SI Loskog
Publication date: 01-12-2012
Publisher: BioMed Central
Published in: Journal of Neuroinflammation / Issue 1/2012
Electronic ISSN: 1742-2094
DOI: https://doi.org/10.1186/1742-2094-9-112

Keynote webinar | Spotlight on medication adherence

Springer Medicine

CAR/FoxP3-engineered T regulatory cells target the CNS and suppress EAE upon intranasal delivery

Abstract

Background

Methods

Results

Conclusion

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Methods

Results

Conclusion

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