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治疗急性移植物抗宿主病的创新方法:临床前靶点和策略综述。

Innovations in treating acute graft-versus-host disease: a review of preclinical targets and strategies.

机构信息

Institute of Blood and Marrow Transplantation, Collaborative Innovation Center of Hematology, Soochow University, Suzhou, China.

Suzhou Medical College, Soochow University, Suzhou, China.

出版信息

Expert Opin Ther Targets. 2024 Sep;28(9):807-824. doi: 10.1080/14728222.2024.2405091. Epub 2024 Sep 19.

Abstract

INTRODUCTION

Acute graft-versus-host disease (aGVHD) is a major complication of post-allogeneic hematopoietic stem cell transplantation (allo-HSCT) that severely impacts patient survival and quality of life. Despite advancements in standard care, therapeutic outcomes remain suboptimal, necessitating the exploration of innovative strategies.

AREAS COVERED

This review synthesizes preclinical research focusing on novel therapeutic targets and strategies that may enhance treatment efficacy. We critically analyzed the role of specific T-cell subsets, cytokine modulators, and intracellular signaling pathways in reducing aGVHD severity. Emphasis is placed on experimental findings that illuminate the mechanisms of immune tolerance and survival improvement. We discuss the translation of these findings into potential clinical trials and evaluate the challenges and progress in implementing these strategies, including scalability and impact on the graft-versus-leukemia (GVL) effect.

EXPERT OPINION

Our review summarizes the latest therapeutic targets and strategies in preclinical research for aGVHD, aiming to bridge the gap between clinical and experimental medicine. By integrating immunology, genetics, and cytology, we seek to enhance the translation of preclinical findings into clinical strategies. This multidisciplinary approach is expected to improve patient outcomes in aGVHD treatment, ultimately leading to more effective and safer therapies.

摘要

简介

急性移植物抗宿主病(aGVHD)是异基因造血干细胞移植(allo-HSCT)后的主要并发症,严重影响患者的生存和生活质量。尽管标准治疗有所进展,但治疗效果仍不理想,因此需要探索创新策略。

涵盖领域

本文综述了专注于新治疗靶点和策略的临床前研究,这些靶点和策略可能提高治疗效果。我们批判性地分析了特定 T 细胞亚群、细胞因子调节剂和细胞内信号通路在减轻 aGVHD 严重程度方面的作用。重点介绍了阐明免疫耐受和生存改善机制的实验发现。我们讨论了将这些发现转化为潜在临床试验的情况,并评估了实施这些策略的挑战和进展,包括可扩展性和对移植物抗白血病(GVL)效应的影响。

专家意见

我们的综述总结了临床前研究中针对 aGVHD 的最新治疗靶点和策略,旨在弥合临床和实验医学之间的差距。通过整合免疫学、遗传学和细胞学,我们力求将临床前发现转化为临床策略。这种多学科方法有望改善 aGVHD 治疗的患者结局,最终带来更有效和更安全的治疗方法。

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