Increased expression of tumor-associated antigens in pediatric and adult ependymomas: implication for vaccine therapy.
Increased expression of tumor-associated antigens in pediatric and adult ependymomas: implication for vaccine therapy.
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DOI：
10.1007/s11060-012-0998-x
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发表时间：
2013-01
影响因子：
3.9
通讯作者：
Pollack, Ian F.
中科院分区：
文献类型：
--
作者：
Yeung, Jacky T.;Hamilton, Ronald L.;Okada, Hideho;Jakacki, Regina I.;Pollack, Ian F.
尽管进行了手术和放疗，但多达50%的室管膜瘤患儿会出现肿瘤复发，最终导致死亡。我们团队最初研发的针对在儿童胶质瘤中过度表达的EphA2、IL - 13Rα2和生存素的基于肽的胶质瘤疫苗，在其初始测试阶段已显示出前景。因此，我们研究了EphA2、IL - 13Rα2、生存素以及威尔姆斯瘤1（WT1）在儿童室管膜瘤中是否过度表达，以确定类似的免疫治疗方法是否适用。我们使用针对EphA2、IL - 13Rα2、生存素和WT1的特异性抗体，对19例儿童和13例成人室管膜瘤的石蜡包埋标本进行了免疫组织化学检测。正常脑组织和室管膜被用作背景染色对照。阴性染色定义为无染色或染色强度等同于正常脑组织中的背景强度。在19例儿童病例中，18例（95%）EphA2染色阳性，16例（84%）IL - 13Rα2染色阳性，18例（95%）生存素染色阳性，而只有7例（37%）WT1染色阳性。19例病例中只有3例对两种或更少的肿瘤相关抗原（TAA）呈阳性；19例病例中有16例对三种或更多的TAA呈阳性。在13例成人病例中，所有13例EphA2、IL - 13Rα2和生存素染色均为阳性。13例病例中只有2例（15%）WT1染色阳性。所有成人标本对三种或更多的TAA呈阳性。一些室管膜瘤在染色强度上表现出斑片状差异。儿童和成人室管膜瘤经常表达EphA2、IL - 13Rα2和生存素。这为在临床试验环境中使用已研发的多肽疫苗治疗室管膜瘤提供了依据。
Despite surgery and radiotherapy, as many as 50 % of children with ependymomas will suffer from tumor recurrences that will ultimately lead to death. Our group’s initial peptide-based glioma vaccine targeting EphA2, IL-13Rα2, and Survivin, which are overexpressed in pediatric gliomas, has shown promise in its initial phase of testing. We therefore investigated whether EphA2, IL-13Raα2, Survivin, and, additionally, Wilms’ Tumor 1 (WT1), are overexpressed in pediatric ependymomas to determine if a similar immunotherapy approach could be applicable. Immunohistochemistry was performed using antibodies specific for EphA2, IL-13Rα2, Survivin, and WT1 on paraffin-embedded specimens from 19 pediatric and 13 adult ependymomas. Normal brain and ependyma were used for background staining controls. Negative staining was defined as no staining or staining equaling the background intensity in normal brain tissues. In the 19 pediatric cases, 18 (95 %) demonstrated positive staining for EphA2, 16 (84 %) for IL-13Rα2, 18 (95 %) for Survivin, and only 7 (37 %) for WT1. Only 3 of 19 cases were positive for two or fewer tumor-associated antigens (TAAs); 16 of 19 cases were positive for three or more TAAs. In the 13 adult cases, all 13 demonstrated positive staining for EphA2, IL-13Rα2, and Survivin. Only 2 of 13 cases (15 %) demonstrated positive staining for WT1. All adult specimens were positive for three or more TAAs. Some ependymomas showed patchy variability in intensity. Pediatric and adult ependymomas frequently express EphA2, IL-13Rα2, and Survivin. This provides the basis for the utilization of an established multiple peptide vaccine for ependymoma in a clinical trial setting.
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影响因子：
7.5
作者：
Nakatsuka, S;Oji, Y;Aozasa, K
通讯作者：
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影响因子：
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Hashiba, Tetsuo;Izumoto, Shuichi;Yoshimine, Toshiki
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Hainfellner, JA
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