Generating Type 1 Regulatory T Cells Through Transcription Factor Targeting

Researchers in the Roncarolo have discovered transcription factors that enable the tracking and differentiation of type 1 T regulatory (Tr1) cells for the treatment of autoimmune conditions.

Type 1 regulatory (Tr1) cells are a subset of T regulatory cells that have been shown in clinical trials to successfully treat graft versus host disease, with the potential to treat other autoimmune diseases as well. Unlike other T regulatory cells, they are not governed by FOXP3 master control and their transcriptional machinery is ill-defined, making it challenging to engineer or induce cells that exhibit their antigen-specific tolerogenic behavior.

Researchers in the Roncarolo lab have discovered key transcription factors that govern the Tr1 cell phenotype via RNA-seq transcriptome analysis. They have proposed a method to utilize these factors to more readily induce Tr1 cell differentiation in vivo or in vitro from CD4+ T cells or iPSCs (induced pluripotent stem cells). While other methods have been described to produce these cells, they are difficult to execute, requiring the coordinated collection of donor CD4+ T cells and recipient monocytes and/or tedious clonal expansion from single cells. This invention simplifies this process, requiring just a single collection of blood and making Tr1 production more robust and scalable for therapeutic use.

Stage of Development

Research in vitro