Development of immuno-monitoring methods and immunotherapy using glioma antigens

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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.