Engineered regulatory T cells expressing myelin-specific chimeric antigen receptors suppress EAE progression

Alessandra De Paula Pohl, Anja Schmidt, Ai Hong Zhang, Tania Maldonado, Christoph Königs, David W. Scott*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

39 Scopus citations

Abstract

The expansion of polyclonal T regulatory cells (Tregs) offers great promise for the treatment of immune-mediated diseases, such as multiple sclerosis (MS). However, polyclonal Tregs can be non-specifically immunosuppressive. Based on the advancements with chimeric antigen receptor (CAR) therapy in leukemia, we previously engineered Tregs to express a T-cell receptor (TCR) specific for a myelin basic protein (MBP) peptide. These TCR-engineered specific Tregs suppressed the proliferation of MBP-reactive T effector cells and ameliorated myelin oligodendrocyte glycoprotein (MOG)-induced experimental autoimmune encephalomyelitis (EAE). Herein, we extend this approach by creating human regulatory T cells expressing functional single-chain chimeric antigen receptors (scFv CAR), targeting either MBP or MOG. These scFv CAR-transduced Tregs retained FoxP3 and Helios, characteristic of Treg cells, after long-term expansion in vitro. Importantly, these engineered CNS targeting CAR-Tregs were able to suppress autoimmune pathology in EAE, demonstrating that these Tregs have the potential to be used as a cellular therapy for MS patients.

Original languageEnglish
Article number104222
JournalCellular Immunology
Volume358
DOIs
StatePublished - Dec 2020
Externally publishedYes

Keywords

  • Chimeric antigen receptor (CAR)
  • EAE
  • Multiple sclerosis
  • Regulatory T cells
  • Single chain (scFv)

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