Hashimoto Naoya, Tsuboi Akihiro, Chiba Yasuyoshi, Izumoto Shuichi, Oka Yoshihiro, Yoshimine Toshiki, Sugiyama Haruo
Department of Neurosurgery, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita-shi, Osaka 565-0871, Japan.
Brain Nerve. 2009 Jul;61(7):805-14.
In this paper, we review the current status of immunotherapy targeting Wilms' tumor 1 (WT1) peptide in malignant brain tumors as well as in other hematological and solid malignancies. WT1 is expressed in various kinds of malignancies, and is involved in oncogenesis. The titers of antibodies against WT1 and the frequency of WT1-specific cytotoxic T lymphocytes (CTLs) were higher in cancer patients than in healthy donors, indicating that WT1 protein has immunogenic function. These findings provided us with a rationale for developing cancer immunotherapy that targets the WT1 peptide. Clinical trials of the WT1 peptide vaccination were initiated, and definite immunological and clinical responses were observed. The disease control rate of 57.1% was obtained especially in the case of recurrent glioblastomas, with a median progression-free survival period of 20.0 weeks and progression-free survival rate at 6 months of 33.3%. The trial showed that WT1 vaccination for malignant gliomas, which is generally believed to be an intractable disease, was safe and elicited a favorable clinical response. Further clinical studies of WT1 vaccination in patients with malignant gliomas as well as other cancers are warranted. An enhancement of the efficacy of WT1 vaccination can be expected with a combined treatment using the WT1-specific helper peptide or anti-cancer chemotherapeutic agents. Administration of WT1 vaccination along with other therapeutic modalities during initial treatment or in the case showing minimal residual disease may prolong the survival time of the cancer patients.
在本文中，我们综述了针对肾母细胞瘤1（WT1）肽的免疫疗法在恶性脑肿瘤以及其他血液系统和实体恶性肿瘤中的现状。WT1在多种恶性肿瘤中表达，并参与肿瘤发生。癌症患者体内抗WT1抗体的滴度和WT1特异性细胞毒性T淋巴细胞（CTL）的频率高于健康供体，这表明WT1蛋白具有免疫原性功能。这些发现为开发针对WT1肽的癌症免疫疗法提供了理论依据。WT1肽疫苗接种的临床试验已经启动，并观察到了明确的免疫和临床反应。特别是在复发性胶质母细胞瘤患者中，疾病控制率达到了57.1%，中位无进展生存期为20.0周，6个月时的无进展生存率为33.3%。该试验表明，针对通常被认为是难治性疾病的恶性胶质瘤进行WT1疫苗接种是安全的，并引发了良好的临床反应。有必要对恶性胶质瘤患者以及其他癌症患者进行WT1疫苗接种的进一步临床研究。使用WT1特异性辅助肽或抗癌化疗药物进行联合治疗有望提高WT1疫苗接种的疗效。在初始治疗期间或在显示微小残留疾病的情况下，将WT1疫苗接种与其他治疗方式联合使用可能会延长癌症患者的生存时间。
