Natural and modified IL-2 for the treatment of cancer and autoimmune diseases
Natural and modified IL-2 for the treatment of cancer and autoimmune diseases
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DOI：
10.1016/j.clim.2018.11.002
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发表时间：
2019-09-01
影响因子：
8.6
通讯作者：
Mizui, Masayuki
中科院分区：
文献类型：
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作者：
Mizui, Masayuki
白细胞介素-2（IL-2）是效应淋巴细胞增殖/分化和调节性T细胞扩增/存活所需的多效性细胞因子。接收IL-2信号的能力由对在每个细胞亚群上表达的不同IL-2受体复合物的亲和力定义。虽然IL-2靶向抗肿瘤细胞毒性淋巴细胞（CTL）用于治疗患有黑色素瘤或肾细胞癌的患者，但针对调节性T（Treg）细胞的IL-2可能在几种免疫相关疾病中具有潜在的治疗价值，包括慢性移植物抗宿主病（cGVHD）、1型糖尿病（T1 D）和系统性红斑狼疮（SLE）。已经进行了多种IL-2改变以将IL-2递送至适当的靶标，包括突变体IL-2、IL-2融合蛋白和抗IL-2抗体。使用IL-2的实验和临床试验正在扩展到包括实体器官移植在内的各种疾病。尽管IL-2应答细胞在控制疾病活动中的可持续性和效率仍不完全清楚，但临床试验的结果将为每种疾病的最有效方案提供基础。
Interleukin-2 (IL-2) is a pleiotropic cytokine required for both effector lymphocyte proliferation/differentiation and regulatory T cell expansion/survival. Ability to receive IL-2 signals is defined by the affinity to distinct IL-2 receptor-complexes expressed on each subset of cells. While IL-2 targets anti-tumor cytotoxic lymphocytes (CTLs) for the treatment of patients with melanoma or renal cell carcinoma, IL-2 directed at regulatory T (Treg) cells could have potential therapeutic value in several immune-related diseases including chronic graft-versus host disease (cGVHD), type 1 diabetes (T1D) and systemic lupus erythematosus (SLE). A variety of IL-2 alteration has been made to deliver IL-2 to the proper target, including mutant IL-2, IL-2-fusion proteins and anti-IL-2 antibodies. Experimental and clinical trials using IL-2 are expanding to diverse group of diseases including solid organ transplantation. Although the sustainability and efficiency of IL-2-responding cells in controlling disease activity are still not fully understood, the results of clinical trials will provide a basis of the most effective regimen for each disease.