Xu Xinyu, Hong Yuxuan, Fan Huanhuan, Guo Zijian
State Key Laboratory of Coordination Chemistry, School of Chemistry and Chemical Engineering, Chemistry and Biomedicine Innovation Center (ChemBIC), Nanjing University, Nanjing, 210023, China.
ChemMedChem. 2024 Jul 15;19(14):e202400111. doi: 10.1002/cmdc.202400111. Epub 2024 May 17.
Abnormally localized nucleic acids (NAs) are considered as pathogen associated molecular patterns (PAMPs) in innate immunity. They are recognized by NAs-specific pattern recognition receptors (PRRs), leading to the activation of associated signaling pathways and subsequent production of type I interferons (IFNs) and pro-inflammatory cytokines, which further trigger the adaptive immunity. Notably, NAs-mediated innate immune activation is highly dependent on the conformation changes, especially the aggregation of PRRs. Evidence indicates that the characteristics of NAs including their length, concentration and even spatial structure play essential roles in inducing the aggregation of PRRs. Therefore, nucleic acid materials (NAMs) with high valency of NAs and high-order structures hold great potential for activating innate and adaptive immunity, making them promising candidates for cancer immunotherapy. In recent years, a variety of NAMs have been developed and have demonstrated significant efficacy in achieving satisfactory anti-tumor immunity in multiple mouse models, exhibiting huge potential for clinical application in cancer treatment. This review aims to discuss the mechanisms of NAMs-mediated innate immune response, and summarize their applications in cancer immunotherapy.
异常定位的核酸（NAs）在固有免疫中被视为病原体相关分子模式（PAMPs）。它们被核酸特异性模式识别受体（PRRs）识别，导致相关信号通路的激活以及随后I型干扰素（IFNs）和促炎细胞因子的产生，这进一步触发适应性免疫。值得注意的是，核酸介导的固有免疫激活高度依赖于构象变化，尤其是模式识别受体的聚集。有证据表明，核酸的特性，包括其长度、浓度甚至空间结构，在诱导模式识别受体聚集方面起着至关重要的作用。因此，具有高核酸价态和高阶结构的核酸材料（NAMs）在激活固有免疫和适应性免疫方面具有巨大潜力，使其成为癌症免疫治疗的有前景的候选物。近年来，已经开发了多种核酸材料，并在多个小鼠模型中实现令人满意的抗肿瘤免疫方面显示出显著疗效，在癌症治疗的临床应用中展现出巨大潜力。本综述旨在讨论核酸材料介导的固有免疫反应机制，并总结它们在癌症免疫治疗中的应用。
