Open AccessNext-generation regulatory T cell therapy
Author(s) -
Leonardo M. R. Ferreira,
Yannick D. Müller,
Jeffrey A. Bluestone,
Qizhi Tang
Publication year - 2019
Publication title -
nature reviews. drug discover/nature reviews. drug discovery
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 9.921
H-Index - 328
eISSN - 1474-1784
pISSN - 1474-1776
DOI - 10.1038/s41573-019-0041-4
Subject(s) - immune system , autoimmunity , cell therapy , chimeric antigen receptor , immunology , genome editing , transplant rejection , medicine , transplantation , t cell , regulatory t cell , immunotherapy , biology , crispr , stem cell , il 2 receptor , microbiology and biotechnology , biochemistry , surgery , gene
Regulatory T cells (T reg cells) are a small subset of immune cells that are dedicated to curbing excessive immune activation and maintaining immune homeostasis. Accordingly, deficiencies in T reg cell development or function result in uncontrolled immune responses and tissue destruction and can lead to inflammatory disorders such as graft-versus-host disease, transplant rejection and autoimmune diseases. As T reg cells deploy more than a dozen molecular mechanisms to suppress immune responses, they have potential as multifaceted adaptable smart therapeutics for treating inflammatory disorders. Indeed, early-phase clinical trials of T reg cell therapy have shown feasibility, tolerability and potential efficacy in these disease settings. In the meantime, progress in the development of chimeric antigen receptors and in genome editing (including the application of CRISPR-Cas9) over the past two decades has facilitated the genetic optimization of primary T cell therapy for cancer. These technologies are now being used to enhance the specificity and functionality of T reg cells. In this Review, we describe the key advances and prospects in designing and implementing T reg cell-based therapy in autoimmunity and transplantation.