Osaka University Graduate School of Medicine, Department of Functional Diagnostic Science, Osaka, Japan.
Jpn J Clin Oncol. 2010 May;40(5):377-87. doi: 10.1093/jjco/hyp194. Epub 2010 Apr 15.
Wilms' tumor gene WT1 encodes a transcription factor and plays an important role in cell growth and differentiation. The WT1 gene is highly expressed in leukemia and various types of solid tumors, whereas WT1 is a tumor marker convenient for the detection of minimal residual disease of leukemia. The WT1 gene was originally defined as a tumor suppressor gene, but we proposed that it was, on the contrary, an oncogene. Furthermore, the WT1 protein has proven to be a promising tumor-associated antigen, in which many human leukocyte antigen class I- or II-restricted WT1 epitopes have been identified. Clinical trials of WT1-targeted immunotherapy have confirmed its safety and clinical efficacy. WT1-specific cytotoxic T lymphocytes and WT1 antibodies are spontaneously induced in tumor-bearing patients, probably because of high immunogenicity of the WT1 protein. WT1-specific cytotoxic T lymphocytes make a major contribution to the graft-versus-leukemia effect after allogenic stem cell transplantation. When 75 cancer antigens including WT1 were prioritized according to several criteria such as therapeutic function and immunogenicity, WT1 was ranked as the top antigen. These findings suggest that a new era of WT1 immunotherapy is imminent.
威尔姆斯瘤基因 WT1 编码一种转录因子，在细胞生长和分化中发挥重要作用。WT1 基因在白血病和各种实体瘤中高度表达，而 WT1 是检测白血病微小残留病的方便肿瘤标志物。WT1 基因最初被定义为肿瘤抑制基因，但我们提出，相反，它是一种癌基因。此外，WT1 蛋白已被证明是一种很有前途的肿瘤相关抗原，其中已经鉴定出许多人类白细胞抗原 I 类或 II 类限制性 WT1 表位。WT1 靶向免疫疗法的临床试验已经证实了其安全性和临床疗效。WT1 特异性细胞毒性 T 淋巴细胞和 WT1 抗体在荷瘤患者中自发产生，可能是由于 WT1 蛋白具有高度的免疫原性。WT1 特异性细胞毒性 T 淋巴细胞在异基因干细胞移植后对移植物抗白血病效应有重要贡献。当根据治疗功能和免疫原性等几个标准对包括 WT1 在内的 75 种癌症抗原进行优先级排序时，WT1 被评为头号抗原。这些发现表明，WT1 免疫治疗的新时代即将到来。
