Division of Hematology, Mayo Clinic, Rochester, MN 55905, USA.
Division of Blood and Marrow Transplant & Cellular Therapy, Department of Pediatrics, University of Minnesota, Minneapolis, MN 55454, USA.
Int J Mol Sci. 2021 Sep 7;22(18):9676. doi: 10.3390/ijms22189676.
Graft-versus-host disease (GVHD) is the leading cause of morbidity and mortality after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Immunomodulation using regulatory T cells (Tregs) offers an exciting option to prevent and/or treat GVHD as these cells naturally function to maintain immune homeostasis, can induce tolerance following HSCT, and have a tissue reparative function. Studies to date have established a clinical safety profile for polyclonal Tregs. Functional enhancement through genetic engineering offers the possibility of improved potency, specificity, and persistence. In this review, we provide the most up to date preclinical and clinical data on Treg cell therapy with a particular focus on GVHD. We discuss the different Treg subtypes and highlight the pharmacological and genetic approaches under investigation to enhance the application of Tregs in allo-HSCT. Lastly, we discuss the remaining challenges for optimal clinical translation and provide insights as to future directions of the field.
移植物抗宿主病（GVHD）是异基因造血干细胞移植（allo-HSCT）后发病率和死亡率的主要原因。使用调节性 T 细胞（Tregs）进行免疫调节为预防和/或治疗 GVHD 提供了一个令人兴奋的选择，因为这些细胞的天然功能是维持免疫稳态，可以在 HSCT 后诱导耐受，并且具有组织修复功能。迄今为止的研究已经为多克隆 Tregs 建立了临床安全性概况。通过基因工程进行功能增强提供了提高效力、特异性和持久性的可能性。在这篇综述中，我们提供了关于 Treg 细胞治疗的最新临床前和临床数据，特别关注 GVHD。我们讨论了不同的 Treg 亚型，并强调了正在研究的药理学和遗传学方法，以增强 Tregs 在 allo-HSCT 中的应用。最后，我们讨论了优化临床转化的剩余挑战，并为该领域的未来方向提供了见解。
