Identification of a human glioma antigen, SOX6, recognized by patients' sera

Ueda, Ryo; Iizuka, Yukihiko; Yoshida, Kazunari; Kawase, Takeshi; Kawakami, Yutaka; Toda, Masahiro

doi:10.1038/sj.onc.1207252

Cited by 62 publications

(56 citation statements)

References 33 publications

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“…SOX2 may also be involved in gastric carcinogenesis (24). Notably, another member of the SOX family, SOX6 was recently identified as a glioma antigen (25). KIAA1344 and NKTR were previously not found to react with sera of cancer patients.…”

Section: Discussionmentioning

confidence: 99%

Complex humoral immune response against a benign tumor: Frequent antibody response against specific antigens as diagnostic targets

Comtesse

Zippel

Walle

et al. 2005

Proc. Natl. Acad. Sci. U.S.A.

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There are numerous studies on the immune response against malignant human tumors. This study was aimed to address the complexity and specificity of humoral immune response against a benign human tumor. We assembled a panel of 62 meningiomaexpressed antigens that show reactivity with serum antibodies of meningioma patients, including 41 previously uncharacterized antigens by screening of a fetal brain expression library. We tested the panel for reactivity with 48 sera, including sera of patients with common-type, atypical, and anaplastic meningioma, respectively. Meningioma sera detected an average of 14.6 antigens per serum and normal sera an average of 7.8 antigens per serum (P ‫؍‬ 0.0001). We found a decline of seroreactivity with malignancy with a statistical significant difference between common-type and anaplastic meningioma (P < 0.05). We detected 17 antigens exclusively with patient sera, including 12 sera that were reactive against KIAA1344, 9 against natural killer tumor recognition (NKTR), and 7 against SRY (sex determining region Y)-box2 (SOX2). More than 80% of meningioma patients had antibodies against at least one of the antigens KIAA1344, SC65, SOX2, and C6orf153. Our results show a highly complex but specific humoral immune response against a benign tumor with a distinct serum reactivity pattern and a decline of complexity with malignancy. The frequent antibody response against specific antigens offers new diagnostic and therapeutic targets for meningioma. We developed a statistical learning method to differentiate sera of meningioma patients from sera of healthy donors. meningioma

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Section: Discussionmentioning

confidence: 99%

Complex humoral immune response against a benign tumor: Frequent antibody response against specific antigens as diagnostic targets

Comtesse

Zippel

Walle

et al. 2005

Proc. Natl. Acad. Sci. U.S.A.

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“…10 Western blot analysis using this antibody revealed that the SOX6 protein was expressed in GL261, but not in EL4 (Fig. 1).…”

Section: Preferential Expression Of Sox6 Protein In Murine Glioma Cellsmentioning

confidence: 99%

“…10 After sequencing, the full length ORF of mouse SOX6 gene from SOX6-pGEM-T Easy Vector was inserted into the pcDNA3 (Invitrogen, Carlsbad, CA; pcDNA3-SOX6). As a control, pcDNA3 plasmid was used as the empty vector (pcDNA3).…”

Section: Construction Of a Sox6 Dna Plasmid And Transfectionmentioning

confidence: 99%

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Induction of protective and therapeutic antitumor immunity by a DNA vaccine with a glioma antigen, SOX6

Ueda¹,

Kinoshita²,

Ito³

et al. 2008

Intl Journal of Cancer

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We previously reported identifying SOX6 as a glioma antigen by serological screening using a testis cDNA library. Its preferential expression and frequent IgG responses in glioma patients indicate that SOX6 may be a useful target for immunotherapy. To examine whether cytotoxic T-lymphocyte (CTL) responses specific for SOX6 to destroy glioma can be generated in vivo, we treated glioma-bearing mice by vaccination with a plasmid DNA encoding murine full-length SOX6 protein. Following SOX6-DNA vaccination, CTLs specific for SOX6-expressing glioma cells were induced, while normal autologous-cells that had restrictedly expressed SOX6 during embryogenesis were not destroyed. Furthermore, DNA vaccination with SOX6 exerted protective and therapeutic antitumor responses in the glioma-bearing mice. This antitumor activity was abrogated by the depletion of CD4 positive T cells and/or CD8 positive T cells. These results suggest that the SOX6 protein has multiple CTL and helper epitopes to induce antitumor activity and the effectiveness of SOX6-DNA vaccine for the prevention and treatment of glioma.

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“…Since generation of tumor reactive T cells are relatively difficult in many cancers in the exception of melanoma, we have applied cDNA expression cloning with sera from cancer patients, called SEREX (serological identification of tumor antigens by cDNA expression cloning), for the identification of tumor antigens in various cancers including melanoma, 7 glioma, 8 colon cancer 9 and bladder cancer. 10 In our study, we isolated tumor antigens using SEREX with sera from patients with pancreatic ductal adenocarcinoma.…”

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confidence: 99%

Immune responses to DNA mismatch repair enzymes hMSH2 and hPMS1 in patients with pancreatic cancer, dermatomyositis and polymyositis

Okada

Noji

Goto

et al. 2005

Intl Journal of Cancer

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To identify tumor antigens useful for diagnosis and immunotherapy of patients with pancreatic ductal adenocarcinoma, we applied a SEREX approach with a cDNA library made from 5 pancreatic cancer cell lines and sera obtained from 8 patients with pancreatic cancer, and isolated total 32 genes, including 14 previously characterized genes and 18 genes with unknown functions. Among these isolated antigens, serum IgG antibodies for 2 isolated DNA mismatch repair enzymes, Homo sapiens mutS homolog 2 (hMSH2) and Homo sapiens postmeiotic segregation increased 1 (hPMS1), were detected in patients with pancreatic ductal adenocarcinoma and dermatomyositis (DM), and polymyositis (PM), but not in sera from healthy individuals. Immunohistochemical study demonstrated that hMSH2 and hPMS1 were over-expressed in pancreatic ductal adenocarcinoma compared to normal pancreatic ducts. These results suggested that hMSH2 and hPMS1 may be useful as CD41 helper T cell antigens for immunotherapy of pancreatic cancer patients and that serum IgG antibodies may be useful for diagnosis of patients with pancreatic ductal adenocarcinoma and DM/PM. ' 2005 Wiley-Liss, Inc.Key words: SEREX; tumor antigens; pancreatic cancer; DNA mismatch repair enzyme Early diagnosis and curative treatment are still difficult for pancreatic ductal adenocarcinoma despite of increased incidence rate.

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Identification of a human glioma antigen, SOX6, recognized by patients' sera

Cited by 62 publications

References 33 publications

Complex humoral immune response against a benign tumor: Frequent antibody response against specific antigens as diagnostic targets

Complex humoral immune response against a benign tumor: Frequent antibody response against specific antigens as diagnostic targets

Induction of protective and therapeutic antitumor immunity by a DNA vaccine with a glioma antigen, SOX6

Immune responses to DNA mismatch repair enzymes hMSH2 and hPMS1 in patients with pancreatic cancer, dermatomyositis and polymyositis

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