Abstract：
Patients with chronic graft versus host disease (cGVHD) have low circulating regulatory T cells (Tregs). Interleukin-2(IL-2) is a growth factor for Tregs, and clinical trials have explored its use in cGVHD patients.
Here we will discuss the biology of IL-2, its rationale for use and results of clinical trials in cGVHD. We also describe its mechanisms of action and alteration in gene expression in T-cell subsets after treatment with low dose IL-2 and photopheresis.
Clinical trials using Low dose IL-2 have been done at single centers in small patient series. The majority of the clinical responses seen with IL-2 in cGVHD are classified as partial responses and efficacy as a single agent is limited. Compared to currently approved oral therapies, it has to be administered subcutaneously and requires specialized processing for compounding and storage limiting its widespread use. Its use is associated with constitutional symptoms and local injection site reactions. Local reactions can be easily managed by supportive care practices like rotation of injection sites and premeditations, constitutional symptoms resolve with, dose reduction (25-50%) allowing for continued therapy. Additional studies are needed to define optimal combination strategies with approved agents. Longer acting formulations of IL-2 that require less frequent dosing may also improve patient compliance.
Here we will discuss the biology of IL-2, its rationale for use and results of clinical trials in cGVHD. We also describe its mechanisms of action and alteration in gene expression in T-cell subsets after treatment with low dose IL-2 and photopheresis.
Clinical trials using Low dose IL-2 have been done at single centers in small patient series. The majority of the clinical responses seen with IL-2 in cGVHD are classified as partial responses and efficacy as a single agent is limited. Compared to currently approved oral therapies, it has to be administered subcutaneously and requires specialized processing for compounding and storage limiting its widespread use. Its use is associated with constitutional symptoms and local injection site reactions. Local reactions can be easily managed by supportive care practices like rotation of injection sites and premeditations, constitutional symptoms resolve with, dose reduction (25-50%) allowing for continued therapy. Additional studies are needed to define optimal combination strategies with approved agents. Longer acting formulations of IL-2 that require less frequent dosing may also improve patient compliance.
摘要：
■患有慢性移植物抗宿主病(cGVHD)的患者具有低循环调节性T细胞(Tregs)。白细胞介素-2（IL-2）是Tregs的生长因子，和临床试验已经探索了其在cGVHD患者中的应用。
■在这里，我们将讨论IL-2的生物学，其使用原理和cGVHD临床试验的结果。我们还描述了用低剂量IL-2和光脱治疗后其作用机制和T细胞亚群基因表达的改变。
■使用低剂量IL-2的临床试验已在小型患者系列的单中心进行。在cGVHD中用IL-2观察到的大多数临床反应被分类为部分反应,并且作为单一药剂的功效是有限的。与目前批准的口服疗法相比，它必须皮下给药，并且需要专门的处理来混合和储存，限制了它的广泛使用。它的使用与体质症状和局部注射部位反应有关。局部反应可以通过支持性护理实践来轻松管理，例如注射部位的轮换和预谋，宪法症状解决，剂量减少（25-50％），允许继续治疗。需要更多的研究来定义与批准的药物的最佳组合策略。需要较低频率给药的更长效IL-2制剂也可以改善患者依从性。
■在这里，我们将讨论IL-2的生物学，其使用原理和cGVHD临床试验的结果。我们还描述了用低剂量IL-2和光脱治疗后其作用机制和T细胞亚群基因表达的改变。
■使用低剂量IL-2的临床试验已在小型患者系列的单中心进行。在cGVHD中用IL-2观察到的大多数临床反应被分类为部分反应,并且作为单一药剂的功效是有限的。与目前批准的口服疗法相比，它必须皮下给药，并且需要专门的处理来混合和储存，限制了它的广泛使用。它的使用与体质症状和局部注射部位反应有关。局部反应可以通过支持性护理实践来轻松管理，例如注射部位的轮换和预谋，宪法症状解决，剂量减少（25-50％），允许继续治疗。需要更多的研究来定义与批准的药物的最佳组合策略。需要较低频率给药的更长效IL-2制剂也可以改善患者依从性。
