[HTML][HTML] Human Tregs made antigen specific by gene modification: the power to treat autoimmunity and antidrug antibodies with precision

PR Adair, YC Kim, AH Zhang, J Yoon… - Frontiers in …, 2017 - frontiersin.org
PR Adair, YC Kim, AH Zhang, J Yoon, DW Scott
Frontiers in immunology, 2017frontiersin.org
Human regulatory CD4+ T cells (Tregs) are potent immunosuppressive lymphocytes
responsible for immune tolerance and homeostasis. Since the seminal reports identifying
Tregs, vast research has been channeled into understanding their genesis, signature
molecular markers, mechanisms of suppression, and role in disease. This research has
opened the doors for Tregs as a potential therapeutic for diseases and disorders such as
multiple sclerosis, type I diabetes, transplantation, and immune responses to protein …
Human regulatory CD4+ T cells (Tregs) are potent immunosuppressive lymphocytes responsible for immune tolerance and homeostasis. Since the seminal reports identifying Tregs, vast research has been channeled into understanding their genesis, signature molecular markers, mechanisms of suppression, and role in disease. This research has opened the doors for Tregs as a potential therapeutic for diseases and disorders such as multiple sclerosis, type I diabetes, transplantation, and immune responses to protein therapeutics, like factor VIII. Seminal clinical trials have used polyclonal Tregs, but the frequency of antigen-specific Tregs among polyclonal populations is low, and polyclonal Tregs may risk non-specific immunosuppression. Antigen-specific Treg therapy, which uses genetically modified Tregs expressing receptors specific for target antigens, greatly mitigates this risk. Building on the principles of T-cell receptor cloning, chimeric antigen receptors (CARs), and a novel CAR derivative, called B-cell antibody receptors, our lab has developed different types of antigen-specific Tregs. This review discusses the current research and optimization of gene-modified antigen-specific human Tregs in our lab in several disease models. The preparations and considerations for clinical use of such Tregs also are discussed.
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