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

Wu,Hongyan; Han,Yu; Qin,Ye; Cao,Chunyu; Xia,Yan; Liu,Changbai; Wang,Yanlin

doi:10.3892/or.2012.2142

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

Authors:
- Hongyan Wu
- Yu Han
- Ye Qin
- Chunyu Cao
- Yan Xia
- Changbai Liu
- Yanlin Wang
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Affiliations: Department of Oncology, Zhongnan Hospital, Wuhan University, Wuhan, Hubei 430071, P.R. China, Institute of Molecular Biology, Three Gorges University Medical College, Yichang, Hubei 443002, P.R. China
Published online on: November 15, 2012 https://doi.org/10.3892/or.2012.2142
Pages: 529-534

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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.

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