Immunopharmacology, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais , Belo Horizonte , Brazil . 55 31 34092649 ;
Expert Opin Ther Targets. 2013 Dec;17(12):1439-60. doi: 10.1517/14728222.2013.837886. Epub 2013 Oct 3.
Chemokines play important roles in inflammation and in immune responses. This article will discuss the current literature on the C-C chemokine ligand 5 (CCL5), and whether it is a therapeutic target in the context of various allergic, autoimmune or infectious diseases.
Small-molecule inhibitors, chemokine and chemokine receptor-deficient mice, antibodies and modified chemokines are the current tools available for CCL5 research, and there are several ongoing clinical trials targeting the CCL5 receptors, CCR1, CCR3 and CCR5. There are fewer studies specifically targeting the chemokine itself and clinical studies with anti-CCL5 antibodies are still to be carried out.
Although clinical trials are strongly biased toward HIV treatment and prevention with blockers of CCR5, the therapeutic potential for CCL5 and its receptors in other diseases is relevant. Overall, it is not likely that specific targeting of CCL5 will result in new adjunct strategies for the treatment of infectious diseases with a major inflammatory component. However, targeting CCL5 could result in novel therapies for chronic inflammatory diseases, where it may decrease inflammatory responses and fibrosis, and certain solid tumors, where it may have a role in angiogenesis.
趋化因子在炎症和免疫反应中发挥着重要作用。本文将讨论关于 C-C 趋化因子配体 5(CCL5)的现有文献,以及它是否是各种过敏、自身免疫或感染性疾病治疗靶点。
小分子抑制剂、趋化因子和趋化因子受体缺失小鼠、抗体和修饰趋化因子是目前用于 CCL5 研究的工具,目前有几个针对 CCL5 受体 CCR1、CCR3 和 CCR5 的临床试验正在进行中。针对趋化因子本身的研究较少,抗 CCL5 抗体的临床研究仍有待开展。
尽管临床试验强烈偏向于使用 CCR5 阻滞剂治疗和预防 HIV,但 CCL5 及其受体在其他疾病中的治疗潜力仍然相关。总的来说,针对 CCL5 的特异性靶向不太可能为具有主要炎症成分的传染病治疗带来新的辅助策略。然而,针对 CCL5 可能会为慢性炎症性疾病带来新的治疗方法,因为它可能会降低炎症反应和纤维化,以及某些实体瘤,因为它可能在血管生成中发挥作用。