Artikel
Identification of SOX2 as a novel glioma-associated antigen and potential target for T cell-based immunotherapy
SOX2 – ein neues Tumor-assoziiertes Antigen in Gliomen
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Veröffentlicht: | 11. April 2007 |
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Gliederung
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Objective: Despite advances in the treatment of malignant glioma the prognosis for patients has not substantially improved. Specific immunotherapy as a novel treatment concept for glioma essentially depends on the identification of target antigens which are expressed in a high percentage of gliomas but not in normal tissues. However, the number of antigens displaying these properties is still very limited. Therefore, we tried to identify new proteins exclusively expressed in glioma tissues.
Methods: Identification of tumor-specific and overexpressed transcripts was accomplished by screening an expression database. Verification of tumor-restricted expression was performed by using cDNA-microarray hybridization, Western Bot analysis and standard immunohistochemistry.
Results: The transcription factor SOX2 (SRY box 2) was found to be overexpressed in glioma. The abundance and specificity of SOX2 mRNA was further investigated in tumor and normal tissues by real time PCR. SOX2 was found to be overexpressed in almost all (9/10) malignant glioma samples as compared to cDNA from pooled normal brain. In 40% of the tumor specimens (4/10), SOX2 was upregulated more than 20-fold. Expression in normal brain and other non-malignant tissues was almost negligible. SOX2 protein expression in glioma cell lines and tissues was verified by Western Blot and immunofluorescence. Immunohistochemical analysis revealed SOX2 protein expression in all malignant glioma tissues investigated ranging from 6% to 66% stained tumor cells.
Conclusions: The abundant and glioma-restricted overexpression of SOX2 recommends this antigen as an attractive target for an antibody-leaded or T cell-based immunotherapy of glioma.