Phase I trial of a multi-epitope-pulsed dendritic cell vaccine for patients with newly diagnosed glioblastoma.
Phase I trial of a multi-epitope-pulsed dendritic cell vaccine for patients with newly diagnosed glioblastoma.
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DOI：
10.1007/s00262-012-1319-0
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发表时间：
2013-01
影响因子：
5.8
通讯作者：
Yu, John S.
中科院分区：
文献类型：
--
作者：
Phuphanich, Surasak;Wheeler, Christopher J.;Rudnick, Jeremy D.;Mazer, Mia;Wang, HongQian;Nuno, Miriam A.;Richardson, Jaime E.;Fan, Xuemo;Ji, Jianfei;Chu, Ray M.;Bender, James G.;Hawkins, Elma S.;Patil, Chirag G.;Black, Keith L.;Yu, John S.
这项研究评估了自体树突状细胞疫苗的安全性和免疫反应，该疫苗使用来自神经胶质瘤上表达的肿瘤相关抗原 (TAA) 的 I 类肽进行脉冲，并在其癌症干细胞群 (ICT-107) 中过度表达。 TAA 表位包括 HER2、TRP-2、gp100、MAGE-1、IL13Rα2 和 AIM-2。 HLA-A1 和/或 HLA-A2 阳性胶质母细胞瘤 (GBM) 患者符合条件。来自白细胞分离术的单核细胞分化为树突状细胞，用TAA肽脉冲，并以两周的间隔皮内施用3次。 21 名患者入组，其中 17 名新诊断的 (ND-GBM) 患者、3 名复发性 GBM 患者和 1 名脑干胶质瘤患者。 15 名新诊断患者的免疫反应数据显示，有 33% 的患者有反应。通过 qRT-PCR 对新鲜冷冻肿瘤样本进行的 TAA 表达显示，所有患者肿瘤均表达至少三种 TAA，其中 75% 表达全部六种 TAA。观察到 PFS 和 OS 增加与 MAGE1 和 AIM-2 定量表达的相关性，并且观察到 gp100 和 HER2 抗原存在更长生存期的趋势。 4 名 HLA-A2+ 患者的复发肿瘤中靶抗原 gp100、HER1 和 IL13Rα2 下调。在接受第二次切除的 5 名患者中发现 CD133 表达减少或缺失。中位随访时间为 40.1 个月，16 名 ND-GBM 患者中有 6 名没有表现出肿瘤复发的证据。新诊断患者的中位 PFS 为 16.9 个月，中位 OS 为 38.4 个月。四种 ICT-107 靶向抗原在疫苗前肿瘤中的表达与 ND-GBM 患者的总生存期和 PFS 延长相关。钆增强肿瘤复发区域中 CD133 表达减少或缺失的观察结果支持了靶向在胶质母细胞瘤癌症干细胞上高表达的肿瘤抗原的目标。
This study evaluated the safety and immune responses to an autologous dendritic cell vaccine pulsed with class I peptides from tumor-associated antigens (TAA) expressed on gliomas and overexpressed in their cancer stem cell population (ICT-107). TAA epitopes included HER2, TRP-2, gp100, MAGE-1, IL13Rα2, and AIM-2. HLA-A1- and/or HLA-A2-positive patients with glioblastoma (GBM) were eligible. Mononuclear cells from leukapheresis were differentiated into dendritic cells, pulsed with TAA peptides, and administered intradermally three times at two-week intervals. Twenty-one patients were enrolled with 17 newly diagnosed (ND-GBM) and three recurrent GBM patients and one brainstem glioma. Immune response data on 15 newly diagnosed patients showed 33 % responders. TAA expression by qRT-PCR from fresh-frozen tumor samples showed all patient tumors expressed at least three TAA, with 75 % expressing all six. Correlations of increased PFS and OS with quantitative expression of MAGE1 and AIM-2 were observed, and a trend for longer survival was observed with gp100 and HER2 antigens. Target antigens gp100, HER1, and IL13Rα2 were downregulated in recurrent tumors from 4 HLA-A2+ patients. A decrease in or absence of CD133 expression was seen in five patients who underwent a second resection. At a median follow-up of 40.1 months, six of 16 ND-GBM patients showed no evidence of tumor recurrence. Median PFS in newly diagnosed patients was 16.9 months, and median OS was 38.4 months. Expression of four ICT-107 targeted antigens in the pre-vaccine tumors correlated with prolonged overall survival and PFS in ND-GBM patients. The goal of targeting tumor antigens highly expressed on glioblastoma cancer stem cells is supported by the observation of decreased or absent CD133 expression in the recurrent areas of gadolinium-enhanced tumors.
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影响因子：
158.5
作者：
Stupp, R;Mason, WP;Ryan, G
通讯作者：
Ryan, G
DOI：
10.1002/stem.102
发表时间：
2009-08
期刊：
Stem cells (Dayton, Ohio)
影响因子：
--
作者：
Xu Q;Liu G;Yuan X;Xu M;Wang H;Ji J;Konda B;Black KL;Yu JS
通讯作者：
Yu JS
影响因子：
3.7
作者：
Irvin DK;Jouanneau E;Duvall G;Zhang XX;Zhai Y;Sarayba D;Seksenyan A;Panwar A;Black KL;Wheeler CJ
通讯作者：
Wheeler CJ
影响因子：
8
作者：
Yuan, XP;Curtin, J;Yu, JS
通讯作者：
Yu, JS
影响因子：
5.2
作者：
Ghods, Ali Jourabcih;Irvin, Dwain;Yu, John S.
通讯作者：
Yu, John S.