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The Next Generation of Pattern Recognition Receptor Agonists: Improving Response Rates in Cancer Immunotherapy.
Current Medicinal Chemistry ( IF 3.5 ) Pub Date : 2020-09-30 , DOI: 10.2174/0929867326666190620103105
Daniel H O' Donovan 1 , Yumeng Mao 1 , Deanna A Mele 2
Affiliation  

The recent success of checkpoint blocking antibodies has sparked a revolution in cancer immunotherapy. Checkpoint inhibition activates the adaptive immune system leading to durable responses across a range of tumor types, although this response is limited to patient populations with pre-existing tumor-infiltrating T cells. Strategies to stimulate the immune system to prime an antitumor response are of intense interest and several groups are now working to develop agents to activate the Pattern Recognition Receptors (PRRs), proteins which detect pathogenic and damageassociated molecules and respond by activating the innate immune response. Although early efforts focused on the Toll-like Receptor (TLR) family of membrane-bound PRRs, TLR activation has been associated with both pro- and antitumor effects. Nonetheless, TLR agonists have been deployed as potential anticancer agents in a range of clinical trials. More recently, the cytosolic PRR Stimulator of IFN Genes (STING) has attracted attention as another promising target for anticancer drug development, with early clinical data beginning to emerge. Besides STING, several other cytosolic PRR targets have likewise captured the interest of the drug discovery community, including the RIG-Ilike Receptors (RLRs) and NOD-like Receptors (NLRs). In this review, we describe the outlook for activators of PRRs as anticancer therapeutic agents and contrast the earlier generation of TLR agonists with the emerging focus on cytosolic PRR activators, both as single agents and in combination with other cancer immunotherapies.



中文翻译:

下一代模式识别受体激动剂:提高癌症免疫治疗的反应率。

检查点阻断抗体的最新成功引发了癌症免疫疗法的一场革命。检查点抑制可激活适应性免疫系统,从而导致对多种肿瘤类型的持久应答,尽管这种应答仅限于具有预先存在的肿瘤浸润T细胞的患者人群。刺激免疫系统引发抗肿瘤反应的策略引起了人们的极大兴趣,现在有数个小组正在研究开发能激活模式识别受体(PRR)的药物,该蛋白可检测致病性和与损伤相关的分子并通过激活先天性免疫应答做出反应。尽管早期的努力集中在膜结合PRR的Toll样受体(TLR)家族,但TLR激活与促肿瘤作用和抗肿瘤作用都有关。尽管如此,在一系列临床试验中,TLR激动剂已被用作潜在的抗癌药。最近,作为早期抗癌药物开发的另一个有希望的靶点,IFN基因的胞质PRR刺激物(STING)引起了人们的注意,并且早期的临床数据开始出现。除STING外,其他几个胞质PRR靶标也引起了药物发现界的兴趣,包括RIG-Ilike受体(RLR)和NOD-样受体(NLR)。在这篇综述中,我们描述了作为抗癌治疗剂的PRR激活剂的前景,并对比了早期的TLR激动剂和新出现的针对细胞溶质PRR激活剂的关注,无论是作为单一药剂还是与其他癌症免疫疗法联合使用。IFN基因的胞质PRR刺激物(STING)作为抗癌药物开发的另一个有希望的目标引起了人们的关注,并且早期的临床数据开始出现。除STING外,其他几个胞质PRR靶标也引起了药物发现界的兴趣,包括RIG-Ilike受体(RLR)和NOD-样受体(NLR)。在这篇综述中,我们描述了作为抗癌治疗剂的PRR激活剂的前景,并对比了早期的TLR激动剂和新出现的针对细胞溶质PRR激活剂的关注,无论是作为单一药剂还是与其他癌症免疫疗法联合使用。IFN基因的胞质PRR刺激物(STING)作为抗癌药物开发的另一个有希望的目标引起了人们的关注,并且早期的临床数据开始出现。除STING外,其他几个胞质PRR靶标也引起了药物发现界的兴趣,包括RIG-Ilike受体(RLR)和NOD-样受体(NLR)。在这篇综述中,我们描述了作为抗癌治疗剂的PRR激活剂的前景,并对比了早期的TLR激动剂和新出现的针对细胞溶质PRR激活剂的关注,无论是作为单一药剂还是与其他癌症免疫疗法联合使用。其他几个胞质PRR靶标也同样引起了药物开发界的关注,包括RIG-Ilike受体(RLR)和NOD-like受体(NLR)。在这篇综述中,我们描述了作为抗癌治疗剂的PRR激活剂的前景,并对比了早期的TLR激动剂和新出现的针对细胞溶质PRR激活剂的关注,无论是作为单一药剂还是与其他癌症免疫疗法联合使用。其他几个胞质PRR靶标也同样引起了药物开发界的关注,包括RIG-Ilike受体(RLR)和NOD-like受体(NLR)。在这篇综述中,我们描述了作为抗癌治疗剂的PRR激活剂的前景,并对比了早期的TLR激动剂和新出现的针对细胞溶质PRR激活剂的关注,无论是作为单一药剂还是与其他癌症免疫疗法联合使用。

更新日期:2020-10-12
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