Myeloid dendritic cells loaded with dendritic tandem multiple antigenic telomerase reverse transcriptase (hTERT) epitope peptides: A potentially promising tumor vaccine

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• 作者：Bai-lin Niu^a ; ¹ ; Hui-min Du^b ; ¹ ; Hua-ping Shen^a ; Zheng-rong Lian^a ; Jin-zheng Li^a ; Xing Lai^a ; Si-dong Wei^a ; Li-quan Zou^c ; ^{zoulq324@sina.com} ; Jian-ping Gong^a ; ^{gongjianping11@126.com}
• 关键词：Ab ; antibody ; APC ; Ag-presenting cell ; BSA ; bovine serum albumin ; C-terminal ; carboxy-terminal ; CTL ; cytotoxic T lymphocyte ; GM-CSF ; granulocyte-macrophage CSF ; HLA ; human histocompatibility leukocyte Ag ; IFN ; interferon ; MACS ; magnetic-activated cell sor
• 刊名：Vaccine
• 出版年：2012
• 期刊代码：89_0264410x
• 类别：imm
• 出版时间：14 May, 2012
• 卷：30
• 期：23
• 页码：3395-3404
• 文件大小：1843 K

摘要

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.