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

研究以WT1为靶点的免疫治疗联合化疗治疗初诊恶性脑胶质瘤的安全性和临床疗效。(1)TMZ/RT联合治疗6周后，外周血中WT1特异性细胞毒T淋巴细胞的比例从0.196%上升到0.256%。TMZ/RT联合治疗6周后，Treg细胞比例由4.8%增加到7.5%，但细胞计数无明显变化。(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”，是安全的。(3)RT-γ法检测WT1特异性辅助性T细胞分泌干扰素和IL-10的情况。在有应答的患者中，在接种前和接种后4周，检测到IL-10型和干扰素-伽玛型WT1(332)特异性Th应答之间存在明显的负相关。(4)WT1免疫治疗联合TMZ化疗是安全的，且产生了免疫应答。

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.