PROTAC 工程化蛋白/DNA 纳米抗原是癌症免疫治疗中树突状细胞疫苗的有效增强剂
PROTAC-Engineered Protein/DNA Nanoantigen is a Potent Booster for Dendritic Cell Vaccines in Cancer Immunotherapy.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
壳聚糖纳米颗粒包被的树突状细胞疫苗作为癌症免疫治疗的影响
英文原题：Impact of Chitosan Nanoparticles-Coated Dendritic Cell-Based Vaccine as Cancer Immunotherapy.
查看英文原题
Impact of Chitosan Nanoparticles-Coated Dendritic Cell-Based Vaccine as Cancer Immunotherapy.
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中文摘要
目的
本研究旨在通过将壳聚糖纳米颗粒（CH-NPs）吸附到 DCs 上，开发一种有效的基于 DC 的抗肿瘤疫苗。
方法
使用细胞因子和脂多糖将未分化的小鼠骨髓祖细胞分化为成熟 DCs。采用离子凝胶法制备 CH-NPs，并随后用于包被刺激后的 DCs。采用 MTT 法评估所有制剂的细胞毒性。为比较 CH-NPs、DCs 和 DCs-CH-NPs 的抗肿瘤效果，将小鼠分为五组并分别注射相应的疫苗制剂。免疫后，使用流式细胞术分析血液和脾脏组织中的 DC 和 CD4 + T 细胞活化。还收集了脾脏和淋巴结的组织学样本。
结果
我们的研究结果表明，在接种疫苗的 DCs 中，共刺激分子 CD80/CD86 和 DC 成熟标志物 CD83 上调，表明其成熟。此外，在体内血液和脾脏样本中，CD83、CD11c 和 MHC-II 上调。与 DCs 组（47.7 ± 11.0）和 CH-NPs 组（37.7 ± 8.6）相比，DC-CH-NPs 疫苗接种组在血液样本中 CD83 表达的平均百分比更高（76.7 ± 17.1）。DC 标志物，尤其是 CD83，在脾脏样本中高表达。此外，与 DCs 组（18.6 ± 1.6）和 CH-NPs 组（13.3 ± 1.4）组。
结论
本研究表明，DC-CH-NPs疫苗制剂能够在体内诱导强烈的免疫反应。这些数据可能为开发有效的抗肿瘤疫苗递送系统提供有价值的见解。
展开英文摘要原文
Dendritic cells (DCs) are major contributors to generating an effective immune response due to their ability to present antigens to T cells. Recently, nanoparticles have been widely used in different medical applications, such as drug-delivery systems, to enhance the function of impaired immune cells. Objectives: This research aims to develop an effective antitumor DC-based vaccine by adsorption of chitosan-nanoparticles (CH-NPs) onto DCs. Methods: Undifferentiated mouse bone marrow progenitor cells were differentiated into mature DCs using cytokines and lipopolysaccharides. CH-NPs were prepared using the ionic gelation method and subsequently used to coat the stimulated DCs.
The MTT assay was employed to assess the cytotoxicity of all formulations. To compare the antitumor effect of CH-NPs, DCs, and DCs-CH-NPs, mice were divided into five groups and injected with the respective vaccine formulations. Following immunization, flow cytometry was used to analyze DC and CD4 + T cell activation in blood and spleen tissues.
Histological samples from the spleen and lymph nodes were also collected. Results: Our findings show that co-stimulatory molecules CD80/CD86 and the DC maturation marker CD83 were upregulated in the vaccinated DCs, indicating their maturation.
Moreover, CD83, CD11c, and MHC-II were upregulated in blood and spleen samples in vivo. The DC-CH-NPs vaccinated group had a higher mean percentage of CD83 expression in blood samples (76. 7 ± 17. 1) compared to the DCs group (47. 7 ± 11. 0) and the CH-NPs group (37. 7 ± 8. 6). DC markers, particularly CD83, were highly expressed in spleen samples.
Additionally, the DC-CH-NPs vaccinated group had a significantly higher number of CD4 + T cells (MFI = 26. 1 ± 2. 3) compared to the DCs (18. 6 ± 1. 6) and CH-NPs (13. 3 ± 1. 4) groups. Conclusions: The present study concludes that the DC-CH-NPs vaccine formulation can induce a potent in vivo immune response. These data may provide valuable insights for developing effective delivery systems for antitumor vaccines.
论文信息
- 作者
- Alrahimi JS、Alotaibi NS、Aldahlawi AM、Basingab FS、Zaher KA
- 第一作者单位
- Department of Biological Sciences, Faculty of Science, King Abdulaziz University, Jeddah 21589, Saudi Arabia.Saudi Arabia
- 通讯作者单位
- Immunology Unit, King Fahd Medical Research Center, King Abdulaziz University, Jeddah 21589, Saudi Arabia.Saudi Arabia
- 期刊
- Vaccines2025 Apr 28
- 原文标识
- PubMed 40432086 · DOI 10.3390/vaccines13050474
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