title: Myeloid dendritic cells loaded with dendritic tandem multiple antigenic telomerase reverse transcriptase (hTERT) epitope peptides: a potentially promising tumor vaccine.
abstract: Human telomerase reverse transcriptase (hTERT) has been identified as an ideal tumor-associated antigen (TAA). Use of a synthetic hTERT epitope peptide to pulse dendritic cells can induce autologous T cell anti-tumor immune responses, but such responses induced by a single epitope peptide have been shown to be weak and a narrow-spectrum. Here, we designed dendritic tandem multiple antigenic peptides (MAPs) containing the following three hTERT epitope peptides: I540, V461 and L766, which are HLA-A*02-, HLA-A*24- and HLA-RDB1*04/11/15-restricted, respectively. The MAPs and their three single-epitope peptides were obtained through solid-phase synthesis. Healthy volunteers that were HLA-A*02(+)/HLA-DRB1*04(+) and HLA-A*24(+)/HLA-DRB1*15(+) were recruited. Myeloid dendritic cells were isolated by magnetic activated cell sorting and were divided into a MAP-stimulated group (MAP-DC), a group in which the three epitope peptides were mixed and used to stimulate the DCs (MixP-DC) and a no peptide-stimulated group (NoP-DC, control group). All of the DCs were cultured in serum-free medium, pulsed with the corresponding peptides on the 3rd, 5th and 7th days, and co-cultured with autologous lymphocytes when they were mature. The related cytokines were measured via ELISA. The killing effects of cytotoxic T lymphocytes (CTLs) on SW480/A549 tumor cells expressing HLA-A*02(+), HepG2/SMMC-7721 cells expressing HLA-A*24(+) and SKOV3 cells negative for HLA-A*02/A*24 were detected by flow cytometry. Our results indicated that the CTLs induced by the MAP-DCs had the greatest anti-tumor effect. Therefore, the dendritic tandem multiple antigenic hTERT epitope peptides combined with MDCs may represent a powerful, broad-spectrum anti-tumor vaccine.
authors.affiliation: Department of Hepatobiliary Surgery, The Second Affiliated Hospital of Chongqing Medical University, Chongqing 400010, China.
authors.forename: Bai-lin
authors.initials: BL
authors.lastname: Niu
authors.forename: Hui-min
authors.initials: HM
authors.lastname: Du
authors.forename: Hua-ping
authors.initials: HP
authors.lastname: Shen
authors.forename: Zheng-rong
authors.initials: ZR
authors.lastname: Lian
authors.forename: Jin-zheng
authors.initials: JZ
authors.lastname: Li
authors.forename: Xing
authors.initials: X
authors.lastname: Lai
authors.forename: Si-dong
authors.initials: SD
authors.lastname: Wei
authors.forename: Li-quan
authors.initials: LQ
authors.lastname: Zou
authors.forename: Jian-ping
authors.initials: JP
authors.lastname: Gong
mesh_terms: D000328:Adult; D019496:Cancer Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D002478:Cells, Cultured; D018920:Coculture Techniques; D003713:Dendritic Cells / Q000276:immunology*; D000939:Epitopes / Q000235:genetics / Q000276:immunology*; D006680:HLA Antigens / Q000235:genetics / Q000276:immunology; D006801:Humans; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D019098:Telomerase / Q000235:genetics / Q000276:immunology*; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology
chemical_list: D019496:Cancer Vaccines; D000939:Epitopes; D006680:HLA Antigens; D014614:Vaccines, Synthetic; C509186:TERT protein, human; D019098:Telomerase