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

研究以WT 1为靶点的免疫治疗联合化疗治疗新诊断恶性胶质瘤的安全性和临床疗效。(1)TMZ/RT联合治疗6周后，血中WT 1特异性细胞毒性T淋巴细胞的频率从0.196%增加到0.256%。TMZ/RT联合治疗6周后，Treg细胞频率从4.8%增加到7.5%，但细胞计数无明显变化。(2)进行了“WT 1免疫疗法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”，并且是安全的。(3)RT-PCR检测WT 1特异性CD 4+辅助性T细胞IFN-γ和IL-10的表达。在有应答的患者中，在接种前和接种后4周检测到IL-10型和IFN-γ型WT 1（332）特异性Th应答之间存在明显的负相关。(4)基于这些结果，WT 1免疫治疗联合TMZ化疗是安全的，并产生了免疫应答。

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.