Krieg Arthur M
Coley Pharmaceutical Group, 93 Worcester Street, Wellesley, MA 02481, USA.
J Clin Invest. 2007 May;117(5):1184-94. doi: 10.1172/JCI31414.
In vertebrates, the TLRs are a family of specialized immune receptors that induce protective immune responses when they detect highly conserved pathogen-expressed molecules. Synthetic agonists for several TLRs, including TLR3, TLR4, TLR7, TLR8, and TLR9, have been or are being developed for the treatment of cancer. TLR9 detects the unmethylated CpG dinucleotides prevalent in bacterial and viral DNA but not in vertebrate genomes. As discussed in this Review, short synthetic oligodeoxynucleotides containing these immune stimulatory CpG motifs activate TLR9 in vitro and in vivo, inducing innate and adaptive immunity, and are currently being tested in multiple phase II and phase III human clinical trials as adjuvants to cancer vaccines and in combination with conventional chemotherapy and other therapies.
在脊椎动物中，Toll样受体（TLR）是一类特殊的免疫受体，当它们检测到高度保守的病原体表达分子时，会诱导保护性免疫反应。包括TLR3、TLR4、TLR7、TLR8和TLR9在内的几种TLR的合成激动剂已被开发或正在开发用于癌症治疗。TLR9可检测细菌和病毒DNA中普遍存在但脊椎动物基因组中不存在的未甲基化CpG二核苷酸。如本综述中所讨论的，含有这些免疫刺激CpG基序的短合成寡脱氧核苷酸在体外和体内均可激活TLR9，诱导先天免疫和适应性免疫，目前正在多项II期和III期人体临床试验中作为癌症疫苗的佐剂以及与传统化疗和其他疗法联合进行测试。
