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

• DOI: 10.1186/1742-2094-9-112
• Publication Date: 2012-07-24T16:15:00Z
• Authors: Moa Fransson; Elena Piras; Joachim Burman; Berith Nilsson; Magnus Essand; BinFeng Lu; Robert A Harris; Peetra U Magnusson; Eva Brittebo; Angelica SI Loskog
• Keywords: Myelin oligodendrocyte glycoprotein; Astrogliosis; Cell therapy; Encephalomyelitis; Regulatory T cell

Multiple sclerosis (MS) is an autoimmune disease of the central nervous system (CNS). In murine experimental encephalomyelitis (EAE) model MS, T regulatory (Treg) cell therapy has proved to be beneficial, but generation stable CNS-targeting Tregs needs further development. Here, we propose gene engineering achieve from naïve CD4 cells and demonstrate their efficacy in EAE model. CD4+ were modified utilizing a lentiviral vector express chimeric antigen receptor (CAR) targeting myelin oligodendrocyte glycoprotein (MOG) trans with FoxP3 that drives Treg differentiation. The evaluated vitro for suppressive capacity C57BL/6 mice treat EAE. Cells administered by intranasal (i.n.) delivery. engineered demonstrated could efficiently access various regions brain via i.n Clinical score 3 treated suppressed ongoing as reduced symptoms well decreased IL-12 IFNgamma mRNAs tissue. Immunohistochemical markers myelination (MBP) reactive astrogliosis (GFAP) confirmed recovery compared controls. Symptom-free rechallenged second EAE-inducing inoculum remained healthy, demonstrating sustained effect Tregs. delivered i.n. localized CNS inflammation leading diminished symptoms.