Regulatory T cell approaches for graft-versus-host disease prevention

作者：Cameron S. Bader, Everett Meyer, Robert S. Negrin · 发表于：Current Opinion in Immunology · 年份：2025 · DOI：10.1016/j.coi.2025.102685 · 被引用次数：4 · 研究领域：T-cell and B-cell Immunology、Hematopoietic Stem Cell Transplantation、vaccines and immunoinformatics approaches

Regulatory T cells (Tregs) are a rare subset of T cells that are potent regulators of the immune system. As a result, the use of Tregs to prevent undesired immune activation and to re-establish immune balance is an attractive cellular therapy approach. In hematopoietic cell transplantation (HCT), there has been significant interest in using Tregs to prevent graft-versus-host disease (GVHD), which occurs when donor alloreactive T cells recognize recipient HLA- or other minor transplantation antigens as non-self. There is a critical unmet need for novel strategies to prevent GVHD since as many as 50% of patients will develop clinically significant GVHD with current therapies. Evidence from preclinical murine models and early-phase human studies suggests that an additional benefit to Treg cellular therapy in HCT is the apparent maintenance of pathogenic immunity and graft-versus-tumor effects, which are required to prevent leukemia relapse. While the major limiting factor for Treg-based therapies has been the rarity of these cells, novel methods to improve Treg isolation and expansion have demonstrated feasibility for implementation of these strategies in the clinic. Moreover, genetic engineering of Tregs has been shown to be a promising strategy to improve their specificity, longevity, and function. Clinical trials have established that such approaches are feasible and can be effective in both human leukocyte antigen (HLA)-matched and haplo-matched settings. In this review, we ...