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Polyethyleneimine‐CpG Nanocomplex as an In Situ Vaccine for Boosting Anticancer Immunity in Melanoma
Macromolecular Bioscience ( IF 4.6 ) Pub Date : 2020-10-26 , DOI: 10.1002/mabi.202000207
Yudi Xu 1, 2 , Sheng Ma 1, 3 , Xinghui Si 1, 4 , Jiayu Zhao 1, 4 , Haiyang Yu 1, 3 , Lili Ma 1, 3 , Wantong Song 1, 3 , Zhaohui Tang 1, 3, 4
Affiliation  

Cancer immunotherapy is redefining the field of cancer therapy. However, current cancer immunotherapies are limited by insufficient immune activation, which results in low response rate. Herein, polyethyleneimine‐CpG nanocomplex (CpG@PEI) is reported as an in situ vaccine for boosting anticancer immunity in melanoma. CpG, a Toll‐like receptor (TLR) 9 agonist, can activate antigen‐presenting cells and increase the expression of costimulatory molecules, while PEI can help to enhance the stability and cellular internalization of CpG. It is proved that PEI loading can significantly enhance the cellular internalization and immune stimulation ability of CpG, and the CpG@PEI nanocomplex can effectively inhibit murine B16F10 melanoma growth after intratumoral injection. Further analysis reveals that this CpG@PEI nanocomplex therapy elicits both innate and adaptive immunity, with much increased natural killer (NK) cells and T cells infiltration in the tumor, as well as CD80 expression on the dendritic cells (DCs). This study will inspire more attempts in directly using single nanoparticle‐loaded pattern recognition receptor (PRR) agonists for cancer immunotherapy.

中文翻译:

聚乙烯亚胺-CpG 纳米复合物作为原位疫苗用于提高黑色素瘤的抗癌免疫力

癌症免疫疗法正在重新定义癌症治疗领域。然而,目前的癌症免疫疗法受到免疫激活不足的限制,导致反应率低。在此,聚乙烯亚胺-CpG 纳米复合物(CpG@PEI)被报道为一种原位疫苗,用于增强黑色素瘤的抗癌免疫力。CpG 是一种 Toll 样受体 (TLR) 9 激动剂,可以激活抗原呈递细胞并增加共刺激分子的表达,而 PEI 可以帮助增强 CpG 的稳定性和细胞内化。证明PEI负载可以显着增强CpG的细胞内化和免疫刺激能力,CpG@PEI纳米复合物可以有效抑制瘤内注射后鼠B16F10黑色素瘤的生长。进一步的分析表明,这种 CpG@PEI 纳米复合物疗法可引发先天免疫和适应性免疫,肿瘤中自然杀伤 (NK) 细胞和 T 细胞浸润显着增加,树突状细胞 (DC) 上的 CD80 表达也显着增加。这项研究将激发更多尝试直接使用单纳米颗粒负载模式识别受体 (PRR) 激动剂进行癌症免疫治疗。
更新日期:2020-10-26
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