Regulatory T cell (Treg)-based immunotherapy is of great interest to induce tolerance in clinical transplantation settings. In fact, the first clinical trials of Treg infusion after stem cell transplantation have recently begun. However, many important issues regarding human Treg immunotherapy are still to be resolved. In this review, we provide a short update on Tregs and elaborate on various strategies for Treg-based immunotherapy. First, infusion of ex vivo-selected naturally occurring Tregs is addressed, with emphasis on Treg isolation, expansion, antigen specificity, homing and stability. Next, the potential of ex vivo-induced Treg transfusion strategies is discussed. Finally, therapies aimed at in vivo increase of Treg numbers or function are addressed. In addition, we summarize the current knowledge on effects of immunosuppressive drugs on Tregs. In the following years, we expect exciting new data regarding the clinical application of Treg immunotherapy in transplantation to be released.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.2217/imt.09.45 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
From promise to practice: CAR T and Treg cell therapies in autoimmunity and other immune-mediated diseases.
Front Immunol
December 2024
Department of Research and Development, Tr1X, Inc., San Diego, CA, United States.
Autoimmune diseases, characterized by the immune system's attack on the body's own tissues, affect millions of people worldwide. Current treatments, which primarily rely on broad immunosuppression and symptom management, are often associated with significant adverse effects and necessitate lifelong therapy. This review explores the next generation of therapies for immune-mediated diseases, including chimeric antigen receptor (CAR) T cell and regulatory T cell (Treg)-based approaches, which offer the prospect of targeted, durable disease remission.
View Article and Find Full Text PDFPreclinical development of a novel CCR8/CTLA-4 bispecific antibody for cancer treatment by disrupting CTLA-4 signaling on CD8 T cells and specifically depleting tumor-resident Tregs.
Cancer Immunol Immunother
August 2024
Mabwell (Shanghai) Bioscience Co., Ltd, Shanghai, 201210, China.
Article Synopsis
- Anti-CTLA-4 antibodies encountered issues like frequent side effects and limited effectiveness, prompting research into advanced CTLA-4 therapies that better deplete regulatory T cells while activating CD8 T cells.
- CCR8, primarily found on tumor-infiltrating Tregs, emerged as a significant target due to its ability to promote anti-tumor responses through Treg depletion.
- The newly developed bispecific antibody 2MW4691 selectively targets CCR8 and CTLA-4, enhancing T cell activation and selectively depleting Tregs, demonstrating promising in vitro and in vivo efficacy with minimal side effects, warranting further clinical trials.
Tregs delivered post-myocardial infarction adopt an injury-specific phenotype promoting cardiac repair via macrophages in mice.
Nat Commun
August 2024
European Molecular Biology Laboratory Australia, Australian Regenerative Medicine Institute, Monash University, Melbourne, Australia.
Regulatory T cells (Tregs) are key immune regulators that have shown promise in enhancing cardiac repair post-MI, although the mechanisms remain elusive. Here, we show that rapidly increasing Treg number in the circulation post-MI via systemic administration of exogenous Tregs improves cardiac function in male mice, by limiting cardiomyocyte death and reducing fibrosis. Mechanistically, exogenous Tregs quickly home to the infarcted heart and adopt an injury-specific transcriptome that mediates repair by modulating monocytes/macrophages.
View Article and Find Full Text PDFRegulation of Treg cells by cytokine signaling and co-stimulatory molecules.
Front Immunol
May 2024
School of Chinese Medicine, Hong Kong Baptist University, Hong Kong, China.
CD4CD25Foxp3 regulatory T cells (Tregs), a vital component of the immune system, are responsible for maintaining immune homeostasis and preventing excessive immune responses. This review explores the signaling pathways of the cytokines that regulate Treg cells, including transforming growth factor beta (TGF-β), interleukin (IL)-2, IL-10, and IL-35, which foster the differentiation and enhance the immunosuppressive capabilities of Tregs. It also examines how, conversely, signals mediated by IL-6 and tumor necrosis factor -alpha (TNF-α) can undermine Treg suppressive functions or even drive their reprogramming into effector T cells.
View Article and Find Full Text PDFBeyond FOXP3: a 20-year journey unravelling human regulatory T-cell heterogeneity.
Front Immunol
January 2024
Center for Regenerative Therapies Dresden, Technical University Dresden, Dresden, Germany.
The initial idea of a distinct group of T-cells responsible for suppressing immune responses was first postulated half a century ago. However, it is only in the last three decades that we have identified what we now term regulatory T-cells (Tregs), and subsequently elucidated and crystallized our understanding of them. Human Tregs have emerged as essential to immune tolerance and the prevention of autoimmune diseases and are typically contemporaneously characterized by their CD3CD4CD25 CD127FOXP3 phenotype.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!