Engineered Tolerance: Tailoring Development, Function, and Antigen-Specificity of Regulatory T Cells

Frontiers in Immunology

Nicholas A. J. Dawson¹  Jens Vent-Schmidt²  Megan K. Levings³ 

[1] BC Children’s Hospital Research Institute, Vancouver, BC, Canada;Department of Medicine, University of British Columbia, Vancouver, BC, Canada;Department of Surgery, University of British Columbia, Vancouver, BC, Canada;

关键词: regulatory T cells;    chimeric antigen receptors;    T cell receptor;    IL-2;    autoimmunity;    transplantation;   

DOI  :  10.3389/fimmu.2017.01460

来源: DOAJ

【 摘 要 】

Regulatory T cells (Tregs) are potent suppressors of immune responses and are currently being clinically tested for their potential to stop or control undesired immune responses in autoimmunity, hematopoietic stem cell transplantation, and solid organ transplantation. Current clinical approaches aim to boost Tregs in vivo either by using Treg-promoting small molecules/proteins and/or by adoptive transfer of expanded Tregs. However, the applicability of Treg-based immunotherapies continues to be hindered by technical limitations related to cell isolation and expansion of a pure, well-characterized, and targeted Treg product. Efforts to overcome these limitations and improve Treg-directed therapies are now under intense investigation in animal models and pre-clinical studies. Here, we review cell and protein engineering-based approaches that aim to target different aspects of Treg biology including modulation of IL-2 signaling or FOXP3 expression, and targeted antigen-specificity using transgenic T cell receptors or chimeric antigen receptors. With the world-wide interest in engineered T cell therapy, these exciting new approaches have the potential to be rapidly implemented and developed into therapies that can effectively fine-tune immune tolerance.

【 授权许可】

Unknown