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使用树突状细胞的全肿瘤抗原疫苗接种:RNA电穿孔与用紫外线照射的肿瘤细胞脉冲处理的比较

Whole tumor antigen vaccination using dendritic cells: comparison of RNA electroporation and pulsing with UV-irradiated tumor cells.

作者信息

Benencia Fabian, Courrèges Maria C, Coukos George

机构信息

Center for Research on Early Detection and Cure of Ovarian Cancer, University of Pennsylvania, Philadelphia, PA, USA.

出版信息

J Transl Med. 2008 Apr 29;6:21. doi: 10.1186/1479-5876-6-21.

Abstract

Because of the lack of full characterization of tumor associated antigens for solid tumors, whole antigen use is a convenient approach to tumor vaccination. Tumor RNA and apoptotic tumor cells have been used as a source of whole tumor antigen to prepare dendritic cell (DC) based tumor vaccines, but their efficacy has not been directly compared. Here we compare directly RNA electroporation and pulsing of DCs with whole tumor cells killed by ultraviolet (UV) B radiation using a convenient tumor model expressing human papilloma virus (HPV) E6 and E7 oncogenes. Although both approaches led to DCs presenting tumor antigen, electroporation with tumor cell total RNA induced a significantly higher frequency of tumor-reactive IFN-gamma secreting T cells, and E7-specific CD8+ lymphocytes compared to pulsing with UV-irradiated tumor cells. DCs electroporated with tumor cell RNA induced a larger tumor infiltration by T cells and produced a significantly stronger delay in tumor growth compared to DCs pulsed with UV-irradiated tumor cells. We conclude that electroporation with whole tumor cell RNA and pulsing with UV-irradiated tumor cells are both effective in eliciting antitumor immune response, but RNA electroporation results in more potent tumor vaccination under the examined experimental conditions.

摘要

由于实体瘤的肿瘤相关抗原缺乏全面的特征描述,使用全抗原是肿瘤疫苗接种的一种便捷方法。肿瘤RNA和凋亡肿瘤细胞已被用作全肿瘤抗原的来源,以制备基于树突状细胞(DC)的肿瘤疫苗,但它们的疗效尚未直接比较。在这里,我们使用表达人乳头瘤病毒(HPV)E6和E7癌基因的便捷肿瘤模型,直接比较了RNA电穿孔以及用紫外线(UV)B辐射杀死的全肿瘤细胞对DC进行脉冲处理的效果。尽管两种方法都能使DC呈递肿瘤抗原,但与用紫外线照射的肿瘤细胞进行脉冲处理相比,用肿瘤细胞总RNA进行电穿孔诱导产生肿瘤反应性IFN-γ分泌T细胞以及E7特异性CD8 +淋巴细胞的频率显著更高。与用紫外线照射的肿瘤细胞进行脉冲处理的DC相比,用肿瘤细胞RNA进行电穿孔的DC诱导T细胞产生更大的肿瘤浸润,并使肿瘤生长延迟显著增强。我们得出结论,用全肿瘤细胞RNA进行电穿孔和用紫外线照射的肿瘤细胞进行脉冲处理在引发抗肿瘤免疫反应方面均有效,但在研究的实验条件下,RNA电穿孔能产生更有效的肿瘤疫苗接种效果。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3f2c/2408561/4dbc4f6e7a7a/1479-5876-6-21-1.jpg

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