In-Depth Review: Chimeric Antigen Receptor T Cell-based Therapies| Volume 187, P53-58, September 2017

Antigen-specific regulatory T cells: are police CARs the answer?

      Cellular therapy with T-regulatory cells (Tregs) is a promising strategy to control immune responses and restore immune tolerance in a variety of immune-mediated diseases, such as transplant rejection and autoimmunity. Multiple clinical trials are currently testing this approach, typically by infusing a single dose of polyclonal Tregs that have been expanded in vitro. However, evidence from animal models of Treg therapy has clearly shown that antigen-specific Tregs are vastly superior to polyclonal cells, meaning that fewer cells are needed for the desired therapeutic effect. Traditional methods to obtain antigen-specific Tregs include antigen-stimulated expansion or T-cell receptor (TCR) overexpression. However, these methods are limited by low cell numbers, complex manufacturing procedures, and knowledge of patient-specific TCRs which recognize disease-relevant MHC-peptide complexes. Recently, several groups have explored the potential to use chimeric antigen receptors (CARs) to generate antigen-specific Tregs. Here, we discuss the progress in this field and highlight the major outstanding questions that remain to be addressed as this approach moves toward clinical applications.


      CEA (carcinoembryonic antigen), CAR (chimeric antigen receptor), EAE (experimental autoimmune encephalomyelitis), HLA (human leukocyte antigen), HSCT (Hematopoietic stem cell transplantation), LAP (latency-associated peptide), PBMC (peripheral blood mononuclear cell), Treg (T-regulatory cells), TCR (T-cell receptor), TGF (Transforming growth factor), TNP (2,4,6-trinitrophenol), TNBS (2,4,6-trinitrobenzene sulfonic acid), WT (wild-type)
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