A novel CD4 T-cell epitope described from one of the cervical cancer patients vaccinated with HPV 16 or 18 E7-pulsed dendritic cells.
A novel CD4 T-cell epitope described from one of the cervical cancer patients vaccinated with HPV 16 or 18 E7-pulsed dendritic cells.
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一种新的 CD4 T 细胞表位，来自一位接种 HPV 16 或 18 E7 脉冲树突状细胞的宫颈癌患者。
DOI：
10.1007/s00262-008-0525-2
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发表时间：
2009
期刊：
影响因子：
--
通讯作者：
Nakagawa,Mayumi
中科院分区：
文献类型：
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作者：
Wang,Xuelian;Santin,AlessandroD;Bellone,Stefania;Gupta,Sushil;Nakagawa,Mayumi
此前，一项剂量递增的 I 期临床试验证明了人乳头瘤病毒 16 型 (HPV16) 或 18 E7 脉冲树突状细胞 (DC) 疫苗的安全性和免疫原性，该试验招募了 10 名诊断为 IB 或 IIA 期宫颈癌的患者（9 名 HPV 16 阳性，1 名 HPV 18 阳性）。该研究的目的是确定这些患者中 HPV 16 或 18 E7 蛋白的 T 细胞表位，以便制定治疗 HPV 相关恶性肿瘤的新策略。这是通过以下方式实现的：用 HPV 16 或 18 E7 蛋白脉冲的自体成熟 DC 刺激外周血单核细胞，使用 ELISPOT 检测检查 T 细胞反应，并根据 IFN-γ 分泌分离 E7 特异性 T 细胞克隆，从而建立 T 细胞系。然后，根据其核心序列和限制性元件对表位进行表征。对来自 8 名受试者（7 名 HPV 16 阳性，1 名 HPV 18 阳性）的 12 个 T 细胞系进行了评估。四名受试者（均为 HPV 16 阳性）显示出阳性 T 细胞反应。所有四种病毒 HPV 16 E7 46-70 (EPDRAHYNIVTFCCKCDSTLRLCVQ) 区域均呈阳性。从其中一名受试者身上分离出 E7 47-70 区域特异的 T 细胞克隆。进一步的分析揭示了一种新的、自然加工的 CD4 T 细胞表位 E7 58-68 (CCKCDSTLRLC)，受到 HLA-DR17 分子的限制。
Previously, safety and immunogenicity of human papillomavirus type 16 (HPV16) or 18 E7-pulsed dendritic cells (DC) vaccinations were demonstrated in a dose-escalation Phase I clinical trial which enrolled ten patients diagnosed with stage IB or IIA cervical cancer (nine HPV 16-positive, one HPV 18-positive). The goal of the study was to define the T-cell epitopes of HPV 16 or 18 E7 protein in these patients in order to develop new strategies for treating HPV-associated malignancies. This was accomplished through establishing T-cell lines by stimulating peripheral blood mononuclear cells with autologous mature DC pulsed with the HPV 16 or 18 E7 protein, examining the T-cell responses using ELISPOT assays, and isolating E7-specific T-cell clones based on IFN-γ secretion. Then, the epitope was characterized in terms of its core sequence and the restriction element. Twelve T-cell lines from eight subjects (seven HPV 16-positive, one HPV 18-positive) were evaluated. Positive T-cell responses were demonstrated in four subjects (all HPV 16-positive). All four were positive for the HPV 16 E7 46-70 (EPDRAHYNIVTFCCKCDSTLRLCVQ) region. T-cell clones specific for the E7 47–70 region were isolated from one of the subjects. Further analyses revealed a novel, naturally processed, CD4 T-cell epitope, E7 58–68 (CCKCDSTLRLC), restricted by the HLA-DR17 molecule.