Trial watch: FDA-approved Toll-like receptor agonists for cancer therapy.
Trial watch: FDA-approved Toll-like receptor agonists for cancer therapy.
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DOI：
10.4161/onci.20931
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发表时间：
2012-09-01
期刊：
影响因子：
7.2
通讯作者：
Kroemer G
中科院分区：
文献类型：
--
作者：
Vacchelli E;Galluzzi L;Eggermont A;Fridman WH;Galon J;Sautès-Fridman C;Tartour E;Zitvogel L;Kroemer G
toll样受体（TLRs）首先以其检测保守微生物成分（如脂多糖（LPS）和双链RNA）的能力而被表征，从而引发针对入侵病原体的有效（先天）免疫反应。最近，tlr也被证明可以促进同源免疫系统对癌细胞的激活。今天，只有三种TLR激动剂被FDA批准用于人类：卡介苗（BCG）、单磷酰脂质A （MPL）和咪喹莫特。卡介苗（牛分枝杆菌的一种减毒菌株）主要用作结核病疫苗，但也用于原位膀胱癌的免疫治疗。MPL（源自明尼苏达沙门氏菌的LPS）包含在Cervarix®的配方中，这是一种针对人乳头瘤病毒-16和-18的疫苗。咪喹莫特（一种合成咪唑喹啉）通常用于光化性角化病、浅表基底细胞癌和外生殖器疣（尖锐湿疣）。在本试验观察中，我们将总结最近完成的临床试验的结果，并讨论正在进行的研究的进展，这些研究已经或正在评估fda批准的TLR激动剂作为癌症治疗的标签外药物。
Toll-like receptors (TLRs) have first been characterized for their capacity to detect conserved microbial components like lipopolysaccharide (LPS) and double-stranded RNA, resulting in the elicitation of potent (innate) immune responses against invading pathogens. More recently, TLRs have also been shown to promote the activation of the cognate immune system against cancer cells. Today, only three TLR agonists are approved by FDA for use in humans: the bacillus Calmette-Guérin (BCG), monophosphoryl lipid A (MPL) and imiquimod. BCG (an attenuated strain of Mycobacterium bovis) is mainly used as a vaccine against tuberculosis, but also for the immunotherapy of in situ bladder carcinoma. MPL (derived from the LPS of Salmonella minnesota) is included in the formulation of Cervarix®, a vaccine against human papillomavirus-16 and -18. Imiquimod (a synthetic imidazoquinoline) is routinely employed for actinic keratosis, superficial basal cell carcinoma, and external genital warts (condylomata acuminata). In this Trial Watch, we will summarize the results of recently completed clinical trials and discuss the progress of ongoing studies that have evaluated/are evaluating FDA-approved TLR agonists as off-label medications for cancer therapy.