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Development of immuno-monitoring methods and immunotherapy using glioma antigens

使用神经胶质瘤抗原开发免疫监测方法和免疫治疗

基本信息

批准号：
15390444
负责人：
TODA Masahiro
金额：
$ 8.96万
依托单位：
Keio University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
2003
资助国家：
日本
起止时间：
2003 至 2005
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-15390444/
关键词：
glioma antigen SOX6 SEREX immunotherapy vaccine CTL T細胞脳腫瘍抗原エピトープ解析免疫モニタリング

项目摘要

In this study, a human testis cDNA library was screened by SEREX (serological identification of antigens by recombinant expression cloning) with sera from glioma patients, we identified a glioma antigen, SOX6, an Sry-related HMG (high mobility group) box-containing gene. IgG antibodies against SOX6 were detected in sera from 12 of 36 glioma patients (33.3%), 0 of 14 patients with other brain disease (0%), and 1 of 54 other cancer patients (1.9%). In sera from 37 healthy individuals, no IgG responses against SOX6 were detected, except in an elderly female. Furthermore, Western blot and ELISA analyses with sera from glioma patients revealed that the DNA-binding domain, the HMG box of SOX6, might be a dominant epitope of IgGs against SOX6. RT-PCR and Northern blot analysis revealed that the SOX6 gene was more highly expressed in glioma tissues than in normal adult tissues, except testis. Immunohistochemical analysis with the anti-SOX6 antibody showed that all the glioma tissues analyzed expressed SOX6 in tumor cells, but only a few SOX6-positive cells were detected in nonneoplastic tissues from the cerebral cortex. By T-cell epitope analysis, we idendified two HLA-A24 restricted peptides derived from SOX6 antigen. Using these epitope peptides, we demonstrated to induce cytotoxic T cells specific for the glioma antigen, SOX6. In summary, we identified a glioma antigen, SOX6, and analyzed the expression pattern, antigen specificity, and T cell epitope of the SOX6.

本研究以人脑胶质瘤患者血清为材料，用SEREX(重组表达克隆法鉴定抗原)筛选人睾丸cDNA文库，鉴定出Sry相关高迁移率族(HMG)盒基因SOX6。36例脑胶质瘤患者中12例(33.3%)、14例其他脑部疾病患者中0例(0%)、54例其他肿瘤患者中1例(1.9%)血清中检测到抗SOX6抗体。在37例健康人血清中，除1例老年女性外，均未检测到抗SOX6的抗体。此外，用胶质瘤患者的血清进行的Western印迹和ELISA分析表明，SOX6的DNA结合域，即HMG盒，可能是抗SOX6的免疫球蛋白的优势表位。RT-PCR和Northern印迹分析表明，SOX6基因在胶质瘤组织中的表达高于正常成人组织(睾丸除外)。抗SOX6抗体免疫组织化学分析显示，所有胶质瘤组织均在肿瘤细胞中表达SOX6，而在大脑皮层非肿瘤组织中仅检测到少量SOX6阳性细胞。通过T细胞表位分析，我们鉴定了两个来源于SOX6抗原的人类白细胞抗原-A24限制性多肽。使用这些表位多肽，我们证明了诱导针对胶质瘤抗原SOX6的细胞毒T细胞。综上所述，我们鉴定了一个胶质瘤抗原SOX6，并分析了SOX6的表达模式、抗原特异性和T细胞表位。