Cancer/Testis Antigens: Structural and Immunobiological Properties

Kirkin, Alexei F.; Dzhandzhugazyan, K.N.; Zeuthen, Jesper

doi:10.1081/cnv-120001150

Cited by 52 publications

(59 citation statements)

References 87 publications

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“…3 In vitro and in vivo experiments have demonstrated that some CT antigens, for example, NY-ESO-1, are capable of provoking potent T-cellmediated immunity to directly kill tumor cells and release cytokines to interfere with the growth of tumor cells, and stimulated antibody response. 12,13 Promising results have been observed in clinical trials using peptide vaccines derived from CT antigens for tumor immunotherapy. 14,15 HCC is the third highest cause of cancer death worldwide with a global incidence of 1.2 million new cases per year.…”

Section: Discussionmentioning

confidence: 99%

Immunohistochemical analysis of the expression of FATE/BJ-HCC-2 antigen in normal and malignant tissues

Yang

Dong

Qiao

et al. 2005

Laboratory Investigation

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FATE/BJ-HCC-2 is a newly identified cancer/testis (CT) antigen, which was detected in tumor tissues and testis. As previous studies of FATE/BJ-HCC-2 expression pattern were mainly based on messenger RNA (mRNA) analysis, it is necessary to investigate its actual protein expression pattern in tumor tissues for the evaluation of its application value. In this study, we produced specific polyclonal antibody (pAb) to the recombinant FATE/ BJ-HCC-2 protein and analyzed the FATE/BJ-HCC-2 antigen expression in normal and malignant tissues by the immunohistochemical approach. The results showed that there was no detectable FATE/BJ-HCC-2 antigen expressed in normal tissues except testis. In hepatocellular carcinoma (HCC) tissues, the FATE/BJ-HCC-2 antigen was detected in 20% (7/35) specimens. All samples that expressed the FATE/BJ-HCC-2 antigen were of poorly or moderately differentiated HCC. The stained antigen was located in the cytoplasm and the staining pattern showed heterogeneity from focal to more than 40% of the tumor cells. The FATE/BJ-HCC-2 antigen was also expressed in other tumor tissues. The results of [ 3 H]thymidine incorporation showed that FATE/BJ-HCC-2 protein enhanced tumor cell proliferation after transfection of FATE/BJ-HCC-2 gene in HCC cell line (Po0.01). This effect could be specifically blocked by anti-FATE/BJ-HCC-2 pAb. Serological screening showed that the antibody specific to the FATE/BJ-HCC-2 antigen was detected in 7.7% (4/52) patients. Notably, the four positive patients bore poorly or moderately differentiated HCC. FATE/BJ-HCC-2 mRNA transcript was detected in the peripheral blood mononuclear cells (PBMCs) of 46.67% patients whose resected HCC tissue samples were positive for FATE/BJ-HCC-2 mRNA, which implicated tumor cell dissemination in blood circulation and may relate to the metastasis of HCC. Thus, FATE/BJ-HCC-2 may be a valuable candidate CT antigen for polyvalent vaccines in tumor immunotherapy and an assisting diagnostic marker for prognosis of the disease.

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Section: Discussionmentioning

confidence: 99%

Immunohistochemical analysis of the expression of FATE/BJ-HCC-2 antigen in normal and malignant tissues

Yang

Dong

Qiao

et al. 2005

Laboratory Investigation

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“…For the restricted expression, CTAs are considered as candidate targets of cancer vaccines (26,27). Immunization against BORIS was shown to be effective in treating mice injected with BORIS-expressing cancer cells (28,29).…”

Section: Ctcfmentioning

confidence: 99%

Transcription Factor BORIS (Brother of the Regulator of Imprinted Sites) Directly Induces Expression of a Cancer-Testis Antigen, TSP50, through Regulated Binding of BORIS to the Promoter

Kosaka-Suzuki¹,

Suzuki²,

Pugacheva

et al. 2011

Journal of Biological Chemistry

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Cancer-testis antigens (CTAs) are normally expressed in testis but are aberrantly expressed in a variety of cancers with varying frequency. More than 100 proteins have been identified as CTA including testes-specific protease 50 (TSP50) and the testis-specific paralogue of CCCTC-binding factor, BORIS (brother of the regulator of imprinted sites). Because many CTAs are considered as excellent targets for tumor immunotherapy, understanding the regulatory mechanisms governing their expression is important. In this study we demonstrate that BORIS is directly responsible for the transcriptional activation of TSP50. We found two BORIS binding sites in the TSP50 promoter that are highly conserved between mouse and human. Mutations of the binding sites resulted in loss of BORIS binding and the ability of BORIS to activate the promoter. However, although expression of BORIS was essential, it was not sufficient for high expression of TSP50 in cancer cells. Further studies showed that binding of BORIS to the target sites was methylation-independent but was diminished by nucleosomal occupancy consistent with the findings that high expression of TSP50 was associated with increased DNase I sensitivity and high BORIS occupancy of the promoter. These findings indicate that BORIS-induced expression of TSP50 is governed by accessibility and binding of BORIS to the promoter. To our knowledge this is the first report of regulated expression of one CTA by another to be validated in a physiological context.

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“…The 'cancer-testis' (CT) antigens are a unique class of antigens that demonstrate high levels of expression in adult male germ cells, but generally not in other normal adult tissues, and aberrant expression in a variable proportion of a wide range of different cancer types (10)(11)(12). This fact makes CT antigens especially attractive targets for specific immunotherapy.…”

Section: Introductionmentioning

confidence: 99%

OY-TES-1 expression and serum immunoreactivity in epithelial ovarian cancer

et al. 2006

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Abstract. OY-TES-1 is a novel target that belongs to the family of 'cancer/testis' (CT) antigens. Our goal was to examine the expression and immunogenicity of OY-TES-1 in epithelial ovarian cancer (EOC) to determine its potential as a target for vaccine therapy. OY-TES-1 expression was determined by one-step reverse transcriptase PCR on 100 EOC samples, 5 EOC cell lines, and a panel of normal tissues. Immunohistochemistry (IHC) was performed on the same panel of EOC tissues. Sera from a sub-group of patients were tested for OY-TES-1 antibody by ELISA. Thymus and leukocytes were weakly positive for OY-TES-1 while the remaining 5 normal tissues were negative. Expression of OY-TES-1 by either RT-PCR and/or IHC was demonstrable in 69/100 (69%) tumors. Humoral immunity to OY-TES-1 was demonstrated in 1/10 (10%) serum samples from patients whose tumors expressed the antigen. The median follow-up of the patient population was 34 months. There was no correlation between antigen expression and stage, grade, histology and survival. OY-TES-1 is expressed in 69% of patients with EOC, is absent from normal ovarian tissue, and a proportion of patients show evidence of a specific humoral immune response. These findings make OY-TES-1 an attractive target for antigen-specific immunotherapy in EOC.

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Cancer/Testis Antigens: Structural and Immunobiological Properties

Cited by 52 publications

References 87 publications

Immunohistochemical analysis of the expression of FATE/BJ-HCC-2 antigen in normal and malignant tissues

Immunohistochemical analysis of the expression of FATE/BJ-HCC-2 antigen in normal and malignant tissues

Transcription Factor BORIS (Brother of the Regulator of Imprinted Sites) Directly Induces Expression of a Cancer-Testis Antigen, TSP50, through Regulated Binding of BORIS to the Promoter

OY-TES-1 expression and serum immunoreactivity in epithelial ovarian cancer

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