Jeong Sehwan, Choi Yunyoung, Kim Kyobum
Department of Chemical & Biochemical Engineering, Dongguk University, 30, Pildong-ro 1-gil, Jung-gu, Seoul 22012, Korea.
Pharmaceutics. 2021 Aug 31;13(9):1374. doi: 10.3390/pharmaceutics13091374.
As a currently spotlighted method for cancer treatment, cancer immunotherapy has made a lot of progress in recent years. Among tremendous cancer immunotherapy boosters available nowadays, Toll-like receptor (TLR) agonists were specifically selected, because of their effective activation of innate and adaptive immune cells, such as dendritic cells (DCs), T cells, and macrophages. TLR agonists can activate signaling pathways of DCs to express CD80 and CD86 molecules, and secrete various cytokines and chemokines. The maturation of DCs stimulates naïve T cells to differentiate into functional cells, and induces B cell activation. Although TLR agonists have anti-tumor ability by activating the immune system of the host, their drawbacks, which include poor efficiency and remarkably short retention time in the body, must be overcome. In this review, we classify and summarize the recently reported delivery strategies using (1) exogenous TLR agonists to maintain the biological and physiological signaling activities of cargo agonists, (2) usage of multiple TLR agonists for synergistic immune responses, and (3) co-delivery using the combination with other immunomodulators or stimulants. In contrast to naked TLR agonists, these exogenous TLR delivery strategies successfully facilitated immune responses and subsequently mediated anti-tumor efficacy.
作为目前备受关注的癌症治疗方法，癌症免疫疗法近年来取得了很大进展。在当今众多的癌症免疫疗法增强剂中，Toll样受体（TLR）激动剂因其能有效激活先天免疫细胞和适应性免疫细胞（如树突状细胞（DC）、T细胞和巨噬细胞）而被特别选用。TLR激动剂可激活DC的信号通路，使其表达CD80和CD86分子，并分泌多种细胞因子和趋化因子。DC的成熟可刺激幼稚T细胞分化为功能细胞，并诱导B细胞活化。尽管TLR激动剂通过激活宿主免疫系统具有抗肿瘤能力，但其缺点（包括效率低下和在体内的保留时间极短）必须克服。在本综述中，我们对最近报道的递送策略进行分类和总结，这些策略包括：（1）使用外源性TLR激动剂以维持货物激动剂的生物学和生理信号活性；（2）使用多种TLR激动剂以产生协同免疫反应；（3）与其他免疫调节剂或刺激剂联合使用进行共递送。与裸TLR激动剂相比，这些外源性TLR递送策略成功促进了免疫反应，并随后介导了抗肿瘤疗效。
