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用重组钙网蛋白包被的全细胞疫苗增强树突状细胞的活化并诱导肿瘤特异性免疫应答。

Whole-cell vaccine coated with recombinant calreticulin enhances activation of dendritic cells and induces tumour-specific immune responses.

机构信息

Department of Oncology, Zhongnan Hospital, Wuhan University, Wuhan, Hubei 430071, PR China.

出版信息

Oncol Rep. 2013 Feb;29(2):529-34. doi: 10.3892/or.2012.2142. Epub 2012 Nov 15.

DOI:10.3892/or.2012.2142
PMID:23166014
Abstract

It has been reported that calreticulin (CRT) plays an important role in mediating immunogenic tumour cell death. In the process of tumour cell apoptosis induced by specific stimuli, CRT is quickly transferred from the endoplasmic reticulum to the cell membrane. As a specific ligand, CRT on the surface of apoptotic tumour cells could mediate the recognition and clearance of apoptotic tumour cells by professional and non-professional phagocytes. In our previous studies, we used B16-F1 mouse melanoma cells coated with mCRT-vGPCR (a recombinant fusion protein of mouse CRT and virus G-protein-coupled receptor) as a whole-cell tumour vaccine to immunise experimental animals and found that this whole-cell vaccine could strongly inhibit the growth of homologous tumours. In this study, we further evaluated immune responses induced by this mCRT-vGPCR-coated whole-cell vaccine both in vivo and in vitro. An in vitro phagocytosis assay showed that the mCRT-vGPCR on the cell surface greatly enhanced the engulfment of B16-F1 cells by dendritic cells (DCs). The specific antitumour immune response was observed when the mCRT-vGPCR-coated B16-F1 cells were used as a whole-cell tumour vaccine to immune mice, which included significantly enhanced cytotoxic T lymphocyte (CTL) activities and increased the number of IFN-γ-producing T cells. These results indicate that the mCRT-vGPCR-coated whole-cell vaccine can induce specific antitumour immunity though the activation of DCs. These results may provide an experimental basis for the development of new tumour vaccines.

摘要

据报道,钙网织蛋白(CRT)在介导免疫原性肿瘤细胞死亡中发挥重要作用。在特定刺激诱导的肿瘤细胞凋亡过程中,CRT 迅速从内质网转移到细胞膜。作为一种特异性配体,凋亡肿瘤细胞表面的 CRT 可介导专业和非专业吞噬细胞对凋亡肿瘤细胞的识别和清除。在我们之前的研究中,我们使用了带有 mCRT-vGPCR(鼠 CRT 和病毒 G 蛋白偶联受体的重组融合蛋白)的 B16-F1 小鼠黑色素瘤细胞作为全细胞肿瘤疫苗来免疫实验动物,发现这种全细胞疫苗能够强烈抑制同源肿瘤的生长。在这项研究中,我们进一步评估了这种 mCRT-vGPCR 包被的全细胞疫苗在体内和体外诱导的免疫反应。体外吞噬试验表明,细胞表面的 mCRT-vGPCR 大大增强了树突状细胞(DC)对 B16-F1 细胞的吞噬作用。当用 mCRT-vGPCR 包被的 B16-F1 细胞作为全细胞肿瘤疫苗免疫小鼠时,观察到了特异性的抗肿瘤免疫反应,包括显著增强的细胞毒性 T 淋巴细胞(CTL)活性和增加 IFN-γ 产生 T 细胞的数量。这些结果表明,mCRT-vGPCR 包被的全细胞疫苗可以通过激活 DC 来诱导特异性抗肿瘤免疫。这些结果可能为新型肿瘤疫苗的开发提供实验依据。

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