Ajou University, Department of Molecular Science and Technology, Suwon 443 749, Korea.
Expert Opin Ther Pat. 2011 Jun;21(6):927-44. doi: 10.1517/13543776.2011.569494. Epub 2011 Mar 15.
The immune response is mediated via two parallel immune components, innate and adaptive, whose effector functions are highly integrated and coordinated for the protection of the human body against invading pathogens and transformed cells. The discovery of pathogen recognition receptors (PRRs), most notably toll-like receptors (TLRs), in innate immunity has evoked increased interest in the therapeutic handling of the innate immune system. TLRs are germ line-encoded receptors that play a potent role in the recognition of a diverse variety of ligands ranging from hydrophilic nucleic acids to lipopolysaccharide (LPS) or peptidoglycan (PGN) structures in pathogens.
This review discusses recent updates (2006-2010) in completed, ongoing and planned clinical trials of TLR immunomodulator-based therapies for the treatment of infectious diseases, inflammatory disorders and cancer.
Since the discovery of human TLRs, modulating immune responses using TLR agonists or antagonists for therapeutic purposes has provoked intense activity in the pharmaceutical industry. The ability of TLRs to initiate and propagate inflammation makes them attractive therapeutic targets. We are now at the stage of evaluating such molecules in human diseases. Additionally, there is also extensive literature available on TLRs in diseased states. These data provide a basis for the identification of novel immunomodulators (agonists and antagonists) for the therapeutic targeting of TLRs.
免疫反应是通过两个平行的免疫成分介导的，先天免疫和适应性免疫，其效应功能高度整合和协调，以保护人体免受入侵病原体和转化细胞的侵害。先天免疫中病原体识别受体（PRRs），尤其是 Toll 样受体（TLRs）的发现，引发了人们对先天免疫系统治疗处理的浓厚兴趣。TLRs 是种系编码的受体，在识别从亲水性核酸到病原体中的脂多糖（LPS）或肽聚糖（PGN）结构等各种配体方面发挥着重要作用。
本综述讨论了 2006 年至 2010 年期间已完成、正在进行和计划进行的 TLR 免疫调节剂治疗传染病、炎症性疾病和癌症的临床试验的最新进展。
自人类 TLRs 的发现以来，使用 TLR 激动剂或拮抗剂调节免疫反应以达到治疗目的，这在制药行业引起了强烈的兴趣。TLRs 引发和传播炎症的能力使其成为有吸引力的治疗靶点。我们现在正处于在人类疾病中评估这些分子的阶段。此外，关于疾病状态下的 TLRs 也有大量文献。这些数据为鉴定用于 TLR 治疗靶向的新型免疫调节剂（激动剂和拮抗剂）提供了基础。
