Investigation of the immunotherapy targeting WT1, and its promoting and inhibiting mechanism in the brain

WT1靶向免疫治疗及其脑内促进和抑制机制研究

• 批准号: 23592148
• 负责人: IZUMOTO SHUICHI
• 金额: $ 3.33万
• 依托单位: Hyogo Medical University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2011
• 资助国家: 日本
• 起止时间: 2011 至 2013
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-23592148/
• 关键词: ＷＴ１; 膠芽腫; 免疫療法; がんワクチン療法

The frequency of WT1-specific cytotoxic T lymphocytes in blood was increased during the WT-1 vaccination for the patients with brain tumors. But the clinical response was divided into 60 % of effected group and 40% of ineffective group. During the combined treatment of TMZ/RT, the frequency of WT1-specific cytotoxic T lymphocytes in blood was increased from 0.196% to 0.256%.Immunohistochemical analysis of the sections obtained by surgery during the WT1 vaccination revealed that WT1-immunodetected cells were both glioma cells and neo-vascular endothelial cells. Accumulation of T cells was divided into two groups. One was the group around the tumor cells and the other was the group near the neo-vascular endothelial cells, those were facilitating the immune response. In the 203G-bearing C57BL6 mouse model, CD4+ and CD8+ T cells were detected but Treg cells were not increased in the brain. In the mouse model, the accumulation of immune cells was not related well with the immune response.

在脑肿瘤患者的WT-1疫苗接种期间，血液中WT-1特异性细胞毒性T淋巴细胞的频率增加。但临床反应分为有效组60%和无效组40%。TMZ/RT联合治疗后，血中WT 1特异性细胞毒性T淋巴细胞的比例从0.196%上升到0.256%;免疫组化结果显示，免疫组化检测到的细胞为胶质瘤细胞和新生血管内皮细胞。将T细胞聚集分为两组。一个是肿瘤细胞周围的一组，另一个是新生血管内皮细胞附近的一组，它们促进了免疫反应。在携带203 G的C57 BL 6小鼠模型中，检测到CD 4+和CD 8 + T细胞，但Treg细胞在脑中没有增加。在小鼠模型中，免疫细胞的积聚与免疫应答没有很好的相关性。

项目成果

初発膠芽腫に対するテモゾロミド併用WT1ペプチドワクチン療法

WT1肽疫苗联合替莫唑胺治疗新诊断的胶质母细胞瘤

• 作者: 橋本直哉;坪井昭博;千葉泰良;香川尚己;泉本修一;平山龍一;岡芳弘;尾路祐介;吉峰俊樹;杉山治夫
• 通讯作者: 杉山治夫