Myeloid dendritic cells loaded with dendritic tandem multiple antigenic telomerase reverse transcriptase (hTERT) epitope peptides: A potentially promising tumor vaccine
Myeloid dendritic cells loaded with dendritic tandem multiple antigenic telomerase reverse transcriptase (hTERT) epitope peptides: A potentially promising tumor vaccine
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DOI：
10.1016/j.vaccine.2012.03.045
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发表时间：
2012-05-14
期刊：
影响因子：
5.5
通讯作者：
Gong, Jian-ping
中科院分区：
文献类型：
--
作者：
Niu, Bai-lin;Du, Hui-min;Gong, Jian-ping
人端粒酶逆转录酶（Human telomerase reverse transcriptase，hTERT）是一种理想的肿瘤相关抗原（tumor associated antigen，TAA）。使用合成的hTERT表位肽来脉冲树突状细胞可以诱导自体T细胞抗肿瘤免疫应答，但是已经显示由单个表位肽诱导的这种应答是弱的和窄谱的。在此，我们设计了树突状串联多抗原肽（MAP），其包含以下三个hTERT表位肽：I540、V461和L766，它们分别是HLA-A*02-、HLA-A*24-和HLA-RDB 1 *04/11/15-限制性的。通过固相合成获得了MAPs及其三个单表位肽。招募HLA-A*02（+）/HLA-DRB 1 *04（+）和HLA-A*24（+）/HLA-DRB 1 *15（+）的健康志愿者。通过磁活化细胞分选分离骨髓树突状细胞，并将其分为MAP刺激组（MAP-DC）、混合三种表位肽并用于刺激DC的组（MixP-DC）和无肽刺激组（NoP-DC，对照组）。所有DC均在无血清培养液中培养，第3、5、7天分别用相应的多肽进行冲击，待DC成熟后与自体淋巴细胞共培养。ELISA法检测相关细胞因子。采用流式细胞术检测细胞毒性T淋巴细胞（CTL）对HLA-A*02（+）表达的SW 480/A549肿瘤细胞、HLA-A*24（+）表达的HepG 2/SMMC-7721细胞和HLA-A*02/A*24阴性的SKOV 3细胞的杀伤作用。我们的成果。表明MAP-DCs诱导的CTL具有最大的抗肿瘤作用。因此，树突状串联多抗原hTERT表位肽与MDCs结合可能代表一种强大的、广谱的抗肿瘤疫苗。(C)2012爱思唯尔有限公司保留所有权利。
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. (C) 2012 Elsevier Ltd. All rights reserved.