A novel peptide targeting Clec9a on dendritic cell for cancer immunotherapy

// Zhongyi Yan 1 , Yahong Wu 1 , Jiangfeng Du 1 , Guodong Li 1 , Shengdian Wang 2 , Wenpeng Cao 1 , Xiuman Zhou 1 , Chunjing Wu 1 , Dan Zhang 1 , Xueli Jing 1 , Yifan Li 1 , Hongfei Wang 1 , Yanfeng Gao 1, 3 , Yuanming Qi 1, 3 1 School of Life Sciences, Zhengzhou University, Zhengzhou, China 2 Institute of Biophysics, Chinese Academy of Sciences, Beijing, China 3 Collaborative 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 Asp 248 and Trp 250 are two key residues for Clec9a to bind with peptide WH. When coupled with OVA 257-264 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-OVA 257-264 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.