Cellular therapies for the prevention and treatment of acute graft-versus-host disease.

IF 4 2区 医学 Q2 BIOTECHNOLOGY & APPLIED MICROBIOLOGY
STEM CELLS Pub Date : 2025-03-21 DOI:10.1093/stmcls/sxaf009
Daniel Peltier, Van Anh Do-Thi, Timothy Devos, Bruce R Blazar, Tomomi Toubai
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Abstract

Acute graft-versus-host disease (aGVHD) is a major complication of allogeneic hematopoietic cell transplantation (allo-HCT) that is caused by donor immune cells attacking and damaging host tissues. Immune suppressive small molecule and protein-based therapeutics targeting donor anti-host immune cells are currently used for GVHD prophylaxis and treatment. Even with these therapies, aGVHD progresses to life-threatening steroid-refractory aGVHD (SR-aGVHD) in up to 50% of cases and is a risk factor for the subsequent development of debilitating chronic GVHD. To improve aGVHD-related outcomes, donor graft engineering techniques and adoptive transfer of immune modulatory cells have been explored. Highly rigorous donor graft T-cell depletion approaches have revealed that mitigation of aGVHD can be accompanied by slow immune recovery post-allo-HCT and reduction in anti-microbial and anti-leukemia responses resulting in increased relapse and infection rates, respectively. Recent T-cell separation techniques allowing for precision graft engineering by selectively eliminating aGVHD-causing T-cells (e.g. naïve T-cells) without loss of T-cells with beneficial functions and retaining and/or enriching immune regulatory populations (e.g. regulatory T-cells (Tregs) or myeloid-derived suppressor cells) have been tested and will continue to improve. Clinical cell-based regulatory therapies have been employed for targeting SR-aGVHD, particularly mesenchymal stem cells (MSCs) and more recently, Tregs. In this review, we summarize aGVHD pathophysiology, highlight newly discovered aGVHD mechanisms, and discuss current and emerging cellular and graft manipulation approaches for aGVHD prevention and treatment.

细胞疗法预防和治疗急性移植物抗宿主病。
急性移植物抗宿主病(aGVHD)是同种异体造血细胞移植(allo-HCT)的主要并发症,由供体免疫细胞攻击和破坏宿主组织引起。针对供体抗宿主免疫细胞的免疫抑制小分子和基于蛋白质的疗法目前用于GVHD的预防和治疗。即使采用这些治疗方法,高达50%的aGVHD病例仍会发展为危及生命的类固醇难治性aGVHD (SR-aGVHD),并且是随后发展为使人衰弱的慢性GVHD的危险因素。为了改善与agvhd相关的结果,研究人员探索了供体移植物工程技术和免疫调节细胞的过继转移。高度严格的供体移植物t细胞耗损方法表明,aGVHD的缓解可能伴随着同种异体造血干细胞移植后缓慢的免疫恢复,以及抗微生物和抗白血病反应的降低,分别导致复发率和感染率的增加。最近的t细胞分离技术允许通过选择性地消除引起agvhd的t细胞(例如naïve t细胞)而不损失具有有益功能的t细胞并保留和/或丰富免疫调节群体(例如调节性t细胞(Tregs)或髓源性抑制细胞)来进行精确移植物工程,已经经过测试并将继续改进。临床基于细胞的调节疗法已被用于靶向SR-aGVHD,特别是间充质干细胞(MSCs)和最近的Tregs。在这篇综述中,我们总结了aGVHD的病理生理,重点介绍了新发现的aGVHD机制,并讨论了目前和新兴的aGVHD预防和治疗的细胞和移植物操作方法。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
STEM CELLS
STEM CELLS 医学-生物工程与应用微生物
CiteScore
10.30
自引率
1.90%
发文量
104
审稿时长
3 months
期刊介绍: STEM CELLS, a peer reviewed journal published monthly, provides a forum for prompt publication of original investigative papers and concise reviews. STEM CELLS is read and written by clinical and basic scientists whose expertise encompasses the rapidly expanding fields of stem and progenitor cell biology. STEM CELLS covers: Cancer Stem Cells, Embryonic Stem Cells/Induced Pluripotent Stem (iPS) Cells, Regenerative Medicine, Stem Cell Technology: Epigenetics, Genomics, Proteomics, and Metabonomics, Tissue-Specific Stem Cells, Translational and Clinical Research.
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