PMID- 27250027 OWN - NLM STAT- MEDLINE DCOM- 20180117 LR - 20181113 IS - 1949-2553 (Electronic) IS - 1949-2553 (Linking) VI - 7 IP - 26 DP - 2016 Jun 28 TI - A novel peptide targeting Clec9a on dendritic cell for cancer immunotherapy. PG - 40437-40450 LID - 10.18632/oncotarget.9624 [doi] AB - 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-gamma, 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. FAU - Yan, Zhongyi AU - Yan Z AD - School of Life Sciences, Zhengzhou University, Zhengzhou, China. FAU - Wu, Yahong AU - Wu Y AD - School of Life Sciences, Zhengzhou University, Zhengzhou, China. FAU - Du, Jiangfeng AU - Du J AD - School of Life Sciences, Zhengzhou University, Zhengzhou, China. FAU - Li, Guodong AU - Li G AD - School of Life Sciences, Zhengzhou University, Zhengzhou, China. FAU - Wang, Shengdian AU - Wang S AD - Institute of Biophysics, Chinese Academy of Sciences, Beijing, China. FAU - Cao, Wenpeng AU - Cao W AD - School of Life Sciences, Zhengzhou University, Zhengzhou, China. FAU - Zhou, Xiuman AU - Zhou X AD - School of Life Sciences, Zhengzhou University, Zhengzhou, China. FAU - Wu, Chunjing AU - Wu C AD - School of Life Sciences, Zhengzhou University, Zhengzhou, China. FAU - Zhang, Dan AU - Zhang D AD - School of Life Sciences, Zhengzhou University, Zhengzhou, China. FAU - Jing, Xueli AU - Jing X AD - School of Life Sciences, Zhengzhou University, Zhengzhou, China. FAU - Li, Yifan AU - Li Y AD - School of Life Sciences, Zhengzhou University, Zhengzhou, China. FAU - Wang, Hongfei AU - Wang H AD - School of Life Sciences, Zhengzhou University, Zhengzhou, China. FAU - Gao, Yanfeng AU - Gao Y AD - School of Life Sciences, Zhengzhou University, Zhengzhou, China. AD - Collaborative Innovation Center of New Drug Research and Safety Evaluation, Zhengzhou, China. FAU - Qi, Yuanming AU - Qi Y AD - School of Life Sciences, Zhengzhou University, Zhengzhou, China. AD - Collaborative Innovation Center of New Drug Research and Safety Evaluation, Zhengzhou, China. LA - eng PT - Journal Article PL - United States TA - Oncotarget JT - Oncotarget JID - 101532965 RN - 0 (Antigens, CD) RN - 0 (CLEC9a protein, human) RN - 0 (Epitopes) RN - 0 (Integrin alpha Chains) RN - 0 (Lectins, C-Type) RN - 0 (Peptides) RN - 0 (Receptors, Mitogen) RN - 0 (alpha E integrins) RN - 82115-62-6 (Interferon-gamma) RN - EC 3.4.21.- (Granzymes) SB - IM MH - Animals MH - Antigen Presentation MH - Antigens, CD/metabolism MH - CD8-Positive T-Lymphocytes/metabolism MH - Cell Line, Tumor MH - Dendritic Cells/*drug effects MH - Epitopes/chemistry MH - Granzymes/metabolism MH - HEK293 Cells MH - Humans MH - Immunotherapy/*methods MH - Integrin alpha Chains/metabolism MH - Interferon-gamma/metabolism MH - Lectins, C-Type/*metabolism MH - Melanoma, Experimental MH - Mice MH - Mice, Inbred C57BL MH - Neoplasm Metastasis MH - Neoplasms/immunology/*therapy MH - Peptides/pharmacology MH - Protein Binding MH - Receptors, Mitogen/*metabolism PMC - PMC5130018 OTO - NOTNLM OT - Clec9a OT - cancer immunotherapy OT - dendritic cells OT - peptide COIS- There are no conflicts of interest to disclosure. EDAT- 2016/10/27 06:00 MHDA- 2018/01/18 06:00 PMCR- 2016/06/28 CRDT- 2016/06/03 06:00 PHST- 2016/02/11 00:00 [received] PHST- 2016/05/09 00:00 [accepted] PHST- 2016/10/27 06:00 [pubmed] PHST- 2018/01/18 06:00 [medline] PHST- 2016/06/03 06:00 [entrez] PHST- 2016/06/28 00:00 [pmc-release] AID - 9624 [pii] AID - 10.18632/oncotarget.9624 [doi] PST - ppublish SO - Oncotarget. 2016 Jun 28;7(26):40437-40450. doi: 10.18632/oncotarget.9624.