Trial Watch: Toll-like receptor agonists in oncological indications.
Trial Watch: Toll-like receptor agonists in oncological indications.
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DOI：
10.4161/onci.29179
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发表时间：
2014
期刊：
影响因子：
7.2
通讯作者：
Galluzzi L
中科院分区：
文献类型：
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作者：
Aranda F;Vacchelli E;Obrist F;Eggermont A;Galon J;Sautès-Fridman C;Cremer I;Henrik Ter Meulen J;Zitvogel L;Kroemer G;Galluzzi L
Toll样受体（TLR）是一组进化上保守的无酶活性的单跨膜蛋白，其识别广泛的外源性和内源性危险信号。除了构成对细菌和病毒病原体的先天免疫应答的关键组分之外，TLR似乎在抗癌免疫监视中发挥主要作用。根据这一概念，已经深入研究了几种天然和合成TLR配体增强由各种免疫疗法和化疗干预引起的肿瘤靶向免疫应答的能力。其中三种药物目前已被美国食品药品监督管理局（FDA）或同等监管机构批准用于癌症患者：所谓的卡介苗、单磷酰脂质A和咪喹莫特。然而，测试FDA批准的和实验性TLR激动剂在癌症患者中的治疗潜力的临床试验数量正在稳定下降，这表明药物开发人员和肿瘤学家正在重新关注替代免疫刺激剂。在这里，我们总结了TLR激动剂在癌症患者中使用的最新发现，并讨论了自我们的第一个试验观察发表以来，FDA批准和实验性TLR配体的临床评价如何发展。
Toll-like receptors (TLRs) are an evolutionarily conserved group of enzymatically inactive, single membrane-spanning proteins that recognize a wide panel of exogenous and endogenous danger signals. Besides constituting a crucial component of the innate immune response to bacterial and viral pathogens, TLRs appear to play a major role in anticancer immunosurveillance. In line with this notion, several natural and synthetic TLR ligands have been intensively investigated for their ability to boost tumor-targeting immune responses elicited by a variety of immunotherapeutic and chemotherapeutic interventions. Three of these agents are currently approved by the US Food and Drug Administration (FDA) or equivalent regulatory agencies for use in cancer patients: the so-called bacillus Calmette-Guérin, monophosphoryl lipid A, and imiquimod. However, the number of clinical trials testing the therapeutic potential of both FDA-approved and experimental TLR agonists in cancer patients is stably decreasing, suggesting that drug developers and oncologists are refocusing their interest on alternative immunostimulatory agents. Here, we summarize recent findings on the use of TLR agonists in cancer patients and discuss how the clinical evaluation of FDA-approved and experimental TLR ligands has evolved since the publication of our first Trial Watch dealing with this topic.
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影响因子：
64.8
作者：
Alexopoulou, L;Holt, AC;Flavell, RA
通讯作者：
Flavell, RA
影响因子：
4.8
作者：
Asea, A;Rehli, M;Calderwood, SK
通讯作者：
Calderwood, SK
影响因子：
3.7
作者：
Castaño-Rodríguez N;Kaakoush NO;Goh KL;Fock KM;Mitchell HM
通讯作者：
Mitchell HM
影响因子：
11.2
作者：
Curran MA;Allison JP
通讯作者：
Allison JP
DOI：
10.1038/nri2587
发表时间：
2009-08
期刊：
Nature reviews. Immunology
影响因子：
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作者：
通讯作者：
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