Oncotarget

Research Papers:

A novel peptide targeting Clec9a on dendritic cell for cancer immunotherapy

Zhongyi Yan _, Yahong Wu, Jiangfeng Du, Guodong Li, Shengdian Wang, Wenpeng Cao, Xiuman Zhou, Chunjing Wu, Dan Zhang, Xueli Jing, Yifan Li, Hongfei Wang, Yanfeng Gao and Yuanming Qi

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Oncotarget. 2016; 7:40437-40450. https://doi.org/10.18632/oncotarget.9624

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Abstract

Zhongyi Yan1, Yahong Wu1, Jiangfeng Du1, Guodong Li1, Shengdian Wang2, Wenpeng Cao1, Xiuman Zhou1, Chunjing Wu1, Dan Zhang1, Xueli Jing1, Yifan Li1, Hongfei Wang1, Yanfeng Gao1,3, Yuanming Qi1,3

1School of Life Sciences, Zhengzhou University, Zhengzhou, China

2Institute of Biophysics, Chinese Academy of Sciences, Beijing, China

3Collaborative Innovation Center of New Drug Research and Safety Evaluation, Zhengzhou, China

Correspondence to:

Yanfeng Gao, email: gaoyf@zzu.edu.cn

Yuanming Qi, email: qym@zzu.edu.cn

Keywords: Clec9a, dendritic cells, cancer immunotherapy, peptide

Received: February 11, 2016    Accepted: May 09, 2016    Published: May 26, 2016

ABSTRACT

Dendritic cells (DCs) are professional antigen-presenting cells with antigen recognition molecules on the surface. Clec9a is selectively expressed on mouse CD8a+ DCs and CD103+ DCs subsets, which are functionally similar to human BDCA3+ DCs. It is reported that Clec9a is responsible for the antigen cross-presentation of these DC subsets. In the present study, by using phage display technique, we discovered a novel peptide WH, which can selectively bind to mouse Flt3L induced Clec9a+ DCs or Clec9a over-expressed HEK-293T cells. Furthermore, by using computer-aided docking model and mutation assay, we observed that Asp248 and Trp250 are two key residues for Clec9a to bind with peptide WH. When coupled with OVA257-264 epitope, peptide WH can significantly enhance the ability of Clec9a+ DCs to activate OVA-specific CD8+ T cells, which elicit strong ability to secret IFN-γ, express perforin and granzyme B mRNA. In B16-OVA lung metastasis mouse model, WH-OVA257-264 fusion peptide can also enhance the activation of CD8+ T cells and decrease the lung metastasis loci. All these results suggested that peptide WH could be considered as an antigen delivery carrier targeting Clec9a+ DCs for cancer immunotherapy.


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