Investigation of the immunotherapy targeting WT1 combined with chemotherapy against newly diagnosed malignant glioma.

WT1靶向免疫治疗联合化疗治疗初诊恶性胶质瘤的研究

• 批准号: 20390384
• 负责人: IZUMOTO Shuichi
• 金额: $ 10.65万
• 依托单位: Hyogo College of Medicine
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2008
• 资助国家: 日本
• 起止时间: 2008 至 2010
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-20390384/
• 关键词: 悪性神経膠腫; 膠芽腫; WT1; 免疫療法; がんワクチン療法; 悪性グリオーマ

The safety and clinical responses of immunotherapy targeting the WT1 combined with chemotherapy against the patients with newly diagnosed malignant glioma were investigated. (1) The frequency of WT1-specific cytotoxic T lymphocytes in blood was increased from 0.196% to 0.256% during the combined treatment of TMZ/RT for 6 weeks. The frequency of Treg cells was increased from 4.8% to 7.5% during the combined treatment of TMZ/RT for 6 weeks, but the cell count was not changed. (2) "Phase I clinical trial of WT1 immunotherapy combined with temozolomide chemotherapy against the patients with newly diagnosed malignant glioma" was performed and was safe. (3) Expression of IFN-γand IL-10 from WT1-specific CD4+ helper T cells were investigated by RT-PCR. In patients who responded, a clear inverse correlation between IL-10-type and IFN-gamma-type WT1(332)-specific Th response was detected at pre- and 4 weeks post-vaccination. (4) Based on these results, WT1 immunotherapy combined with TMZ chemotherapy was safe and produced a immune-response.

研究了以WT1为靶点的免疫治疗联合化疗治疗新诊断的恶性胶质瘤患者的安全性和临床反应。(1) TMZ/RT联合治疗6周后，患者血液中wt1特异性细胞毒性T淋巴细胞的频率由0.196%升高至0.256%。TMZ/RT联合治疗6周后，Treg细胞的出现频率从4.8%增加到7.5%，但细胞数量没有变化。(2)“WT1免疫治疗联合替莫唑胺化疗治疗新诊断恶性胶质瘤患者的I期临床试验”进行且安全。(3)采用RT-PCR检测wt1特异性CD4+辅助性T细胞中IFN-γ和IL-10的表达。在应答的患者中，在接种前和接种后4周检测到il -10型和ifn - γ型WT1（332）特异性Th应答之间存在明显的负相关。(4)基于这些结果，WT1免疫治疗联合TMZ化疗是安全的，并产生了免疫应答。

项目成果

Immunohistocheraical analysis of adhesion molecules and matrix metalloproteinases in malignant CNS lymphomas : a study comparing primary CNS malignant and CNS intravascular lymphomas.

恶性中枢神经系统淋巴瘤中粘附分子和基质金属蛋白酶的免疫组织化学分析：一项比较原发性中枢神经系统恶性淋巴瘤和中枢神经系统血管内淋巴瘤的研究。

• 发表时间: 2008
• 期刊: Brain Tumor Pathol. 25
• 作者: Kinoshita;M
• 通讯作者: M

成人CNS PNETと幼児期PNETとの臨床病理学的相違とIDH1遺伝子変異

成人 CNS PNET 和儿童 PNET 之间的临床病理差异和 IDH1 基因突变

• 发表时间: 2009
• 作者: 広瀬雄一;佐々木光;三輪点;佐野公俊;Ishigaki D;平松匡文;泉本修一
• 通讯作者: 泉本修一

WT1 (Wilms tumor gene)peptide vaccination for patients with recurrent glioblastoma.

WT1（Wilms 肿瘤基因）肽疫苗接种用于复发性胶质母细胞瘤患者。

• 发表时间: 2008
• 作者: Yamanaka R;Kajiwara K;Sagiu K;伊達勲;Izumoto S
• 通讯作者: Izumoto S

A clear correlation between WT1-specific Th response and clinical response in WT1 CTL epitope vaccination.

WT1 特异性 Th 反应与 WT1 CTL 表位疫苗接种中的临床反应之间存在明显相关性。

• 发表时间: 2010
• 期刊: Anticancer Res 30
• 作者: Fujiki F;Tsuboi A;Izumoto S
• 通讯作者: Izumoto S

A surgically treated case of Lhermitte-Duclos disease with a precise natural history and high uptake of FDG on PET

• DOI: 10.1007/s11060-009-0042-y
• 发表时间: 2010-05-01
• 期刊: JOURNAL OF NEURO-ONCOLOGY
• 影响因子: 3.9
• 作者: Goto, Yuko;Hashimoto, Naoya;Yoshimine, Toshiki
• 通讯作者: Yoshimine, Toshiki