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树突状细胞疫苗与负载白细胞介素-15 和抗β-catenin siRNA 的纳米颗粒联合肿瘤免疫治疗显著抑制肿瘤生长并诱导抗肿瘤免疫应答

英文原题:Combination Cancer Immunotherapy with Dendritic Cell Vaccine and Nanoparticles Loaded with Interleukin-15 and Anti-beta-catenin siRNA Significantly Inhibits Cancer Growth and Induces Anti-Tumor Immune Response.

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Combination Cancer Immunotherapy with Dendritic Cell Vaccine and Nanoparticles Loaded with Interleukin-15 and Anti-beta-catenin siRNA Significantly Inhibits Cancer Growth and Induces Anti-Tumor Immune Response.

PubMed 2022/02/15(内容时间) Pharm Res Q2 · IF 4.1(JCR 2025)

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研究概要

这些发现表明,使用 SPION-C-CMD-FA 等新型纳米载体,可能是将β-catenin siRNA、IL-15 和 DC 疫苗组成的新型联合疗法用于治疗癌症的有效途径。

研究思路结论见上方概要

新型免疫治疗方法的发明和应用可以弥补传统癌症治疗方法的低效性,部分原因是肿瘤的抑制性微环境。在本研究中,我们试图通过沉默肿瘤微环境中β-catenin的表达并传递白细胞介素(IL)-15细胞因子,为树突状细胞(DC)疫苗提供最佳条件,从而抑制癌细胞的生长并诱导抗肿瘤免疫反应。

为此,我们使用叶酸(FA)偶联的SPION-羧甲基葡聚糖(CMD)壳聚糖(C)纳米颗粒(NPs)将抗β-catenin siRNA和IL-15递送至癌细胞。

结果显示,β-catenin siRNA与IL-15的共递送显著降低了癌细胞的生长并增强了免疫反应。该治疗还显著促进了DC疫苗在激发抗肿瘤免疫方面的表现,从而在两种不同的癌症模型中抑制了肿瘤发展并提高了小鼠的生存率。

展开英文摘要原文

The invention and application of new immunotherapeutic methods can compensate for the inefficiency of conventional cancer treatment approaches, partly due to the inhibitory microenvironment of the tumor. In this study, we tried to inhibit the growth of cancer cells and induce anti-tumor immune responses by silencing the expression of the β-catenin in the tumor microenvironment and transmitting interleukin (IL)-15 cytokine to provide optimal conditions for the dendritic cell (DC) vaccine.

For this purpose, we used folic acid (FA)-conjugated SPION-carboxymethyl dextran (CMD) chitosan (C) nanoparticles (NPs) to deliver anti-β-catenin siRNA and IL-15 to cancer cells.

The results showed that the codelivery of β-catenin siRNA and IL-15 significantly reduced the growth of cancer cells and increased the immune response. The treatment also considerably stimulated the performance of the DC vaccine in triggering anti-tumor immunity, which inhibited tumor development and increased survival in mice in two different cancer models.

These findings suggest that the use of new nanocarriers such as SPION-C-CMD-FA could be an effective way to use as a novel combination therapy consisting of β-catenin siRNA, IL-15, and DC vaccine to treat cancer.

论文信息

作者
Kheshti AMS、Hajizadeh F、Barshidi A、Rashidi B、Ebrahimi F、Bahmanpour S、Karpisheh V、Noukabadi FK
第一作者单位
Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.Iran
通讯作者单位
Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran. jadidif@tbzmed.ac.ir.Iran
文献类型
已撤稿
期刊
Pharmaceutical research2022 Feb
原文标识
PubMed 35166995 · DOI 10.1007/s11095-022-03169-2