CpG Oligonucleotides as Cancer Vaccine Adjuvants.
CpG Oligonucleotides as Cancer Vaccine Adjuvants.
复制标题
DOI：
10.3390/vaccines3020390
复制
发表时间：
2015-05-08
期刊：
影响因子：
7.8
通讯作者：
Klinman DM
中科院分区：
文献类型：
--
作者：
Shirota H;Tross D;Klinman DM
佐剂通过多种机制提高宿主对共递送疫苗的应答性。触发表达Toll样受体（TLR）的细胞的试剂激活先天免疫应答，其增强疫苗特异性免疫的诱导。当与设计用于预防或减缓肿瘤生长的疫苗组合施用时，TLR激动剂显著改善了细胞毒性T淋巴细胞的产生。不幸的是，含有TLR激动剂的疫苗在全身施用时很少能够消除大的已建立的肿瘤。为了提高疗效，人们的注意力集中在肿瘤内递送TLR激动剂，以改变肿瘤微环境。靶向TLR 7/8或9的激动剂可以降低TGFAP的频率，同时引起肿瘤床中的免疫抑制性MDSC分化成杀肿瘤巨噬细胞，从而增强肿瘤消除。本文综述了TLR 7/8/9激动剂作为肿瘤疫苗佐剂的临床前和临床研究。
Adjuvants improve host responsiveness to co-delivered vaccines through a variety of mechanisms. Agents that trigger cells expressing Toll-like receptors (TLR) activate an innate immune response that enhances the induction of vaccine-specific immunity. When administered in combination with vaccines designed to prevent or slow tumor growth, TLR agonists have significantly improved the generation of cytotoxic T lymphocytes. Unfortunately, vaccines containing TLR agonists have rarely been able to eliminate large established tumors when administered systemically. To improve efficacy, attention has focused on delivering TLR agonists intra-tumorally with the intent of altering the tumor microenvironment. Agonists targeting TLRs 7/8 or 9 can reduce the frequency of Tregs while causing immunosuppressive MDSC in the tumor bed to differentiate into tumoricidal macrophages thereby enhancing tumor elimination. This work reviews pre-clinical and clinical studies concerning the utility of TLR 7/8/9 agonists as adjuvants for tumor vaccines.