Oka Yoshihiro, Tsuboi Akihiro, Oji Yusuke, Kawase Ichiro, Sugiyama Haruo
Department of Respiratory Medicine, Allergy and Rheumatic Diseases, Osaka University Graduate School of Medicine, Japan.
Curr Opin Immunol. 2008 Apr;20(2):211-20. doi: 10.1016/j.coi.2008.04.009. Epub 2008 May 24.
Wilms' tumor gene WT1 is expressed in various kinds of cancers. Human WT1-specific cytotoxic T lymphocytes (CTLs) were generated, and mice immunized with WT1 peptide rejected challenges by WT1-expressing cancer cells without auto-aggression to normal organs. Furthermore, WT1 antibodies and WT1-specific CTLs were detected in cancer patients, indicating that WT1 protein was immunogenic. These findings provided us with the rationale for cancer immunotherapy targeting WT1. Clinical trials of WT1 peptide vaccination for cancer patients were started, and WT1 vaccination-related immunological responses and clinical responses, including reduction of leukemic cells, reduction of M-protein amount in myeloma, and shrinkage of solid cancer, were observed. Valuable information about immune responses against tumor antigens can be obtained by the analysis of samples from the vaccinated patients, which should lead to further improvement of cancer vaccine.
肾母细胞瘤基因WT1在多种癌症中表达。已产生人WT1特异性细胞毒性T淋巴细胞（CTL），用WT1肽免疫的小鼠能够抵抗表达WT1的癌细胞的攻击，且不会对正常器官产生自身攻击。此外，在癌症患者中检测到WT1抗体和WT1特异性CTL，这表明WT1蛋白具有免疫原性。这些发现为针对WT1的癌症免疫治疗提供了理论依据。针对癌症患者的WT1肽疫苗接种临床试验已经启动，并且观察到了与WT1疫苗接种相关的免疫反应和临床反应，包括白血病细胞减少、骨髓瘤中M蛋白量减少以及实体癌缩小。通过分析接种疫苗患者的样本，可以获得有关针对肿瘤抗原的免疫反应的有价值信息，这应该会导致癌症疫苗的进一步改进。
