title: A novel peptide targeting Clec9a on dendritic cell for cancer immunotherapy.
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.
authors.affiliation: School of Life Sciences, Zhengzhou University, Zhengzhou, China.
authors.forename: Zhongyi
authors.initials: Z
authors.lastname: Yan
authors.affiliation: School of Life Sciences, Zhengzhou University, Zhengzhou, China.
authors.forename: Yahong
authors.initials: Y
authors.lastname: Wu
authors.affiliation: School of Life Sciences, Zhengzhou University, Zhengzhou, China.
authors.forename: Jiangfeng
authors.initials: J
authors.lastname: Du
authors.affiliation: School of Life Sciences, Zhengzhou University, Zhengzhou, China.
authors.forename: Guodong
authors.initials: G
authors.lastname: Li
authors.affiliation: Institute of Biophysics, Chinese Academy of Sciences, Beijing, China.
authors.forename: Shengdian
authors.initials: S
authors.lastname: Wang
authors.affiliation: School of Life Sciences, Zhengzhou University, Zhengzhou, China.
authors.forename: Wenpeng
authors.initials: W
authors.lastname: Cao
authors.affiliation: School of Life Sciences, Zhengzhou University, Zhengzhou, China.
authors.forename: Xiuman
authors.initials: X
authors.lastname: Zhou
authors.affiliation: School of Life Sciences, Zhengzhou University, Zhengzhou, China.
authors.forename: Chunjing
authors.initials: C
authors.lastname: Wu
authors.affiliation: School of Life Sciences, Zhengzhou University, Zhengzhou, China.
authors.forename: Dan
authors.initials: D
authors.lastname: Zhang
authors.affiliation: School of Life Sciences, Zhengzhou University, Zhengzhou, China.
authors.forename: Xueli
authors.initials: X
authors.lastname: Jing
authors.affiliation: School of Life Sciences, Zhengzhou University, Zhengzhou, China.
authors.forename: Yifan
authors.initials: Y
authors.lastname: Li
authors.affiliation: School of Life Sciences, Zhengzhou University, Zhengzhou, China.
authors.forename: Hongfei
authors.initials: H
authors.lastname: Wang
authors.affiliation: School of Life Sciences, Zhengzhou University, Zhengzhou, China.|Collaborative Innovation Center of New Drug Research and Safety Evaluation, Zhengzhou, China.
authors.forename: Yanfeng
authors.initials: Y
authors.lastname: Gao
authors.affiliation: School of Life Sciences, Zhengzhou University, Zhengzhou, China.|Collaborative Innovation Center of New Drug Research and Safety Evaluation, Zhengzhou, China.
authors.forename: Yuanming
authors.initials: Y
authors.lastname: Qi
mesh_terms: D000818:Animals; D017951:Antigen Presentation; D015703:Antigens, CD / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism; D045744:Cell Line, Tumor; D003713:Dendritic Cells / Q000187:drug effects*; D000939:Epitopes / Q000737:chemistry; D053804:Granzymes / Q000378:metabolism; D057809:HEK293 Cells; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D039001:Integrin alpha Chains / Q000378:metabolism; D007371:Interferon-gamma / Q000378:metabolism; D037181:Lectins, C-Type / Q000378:metabolism*; D008546:Melanoma, Experimental; D051379:Mice; D008810:Mice, Inbred C57BL; D009362:Neoplasm Metastasis; D009369:Neoplasms / Q000276:immunology / Q000628:therapy*; D010455:Peptides / Q000494:pharmacology; D011485:Protein Binding; D011975:Receptors, Mitogen / Q000378:metabolism*
chemical_list: D015703:Antigens, CD; C530206:CLEC9a protein, human; D000939:Epitopes; D039001:Integrin alpha Chains; D037181:Lectins, C-Type; D010455:Peptides; D011975:Receptors, Mitogen; C091367:alpha E integrins; D007371:Interferon-gamma; D053804:Granzymes
keywords: Clec9a; cancer immunotherapy; dendritic cells; peptide