Genomic cloning and localization of CTAG, a gene encoding an autoimmunogenic cancer-testis antigen NY-ESO-1 to human chromosome Xq28

Chen, Y.-T.; Boyer, Antonia; Viars, Carrie S.; Tsang, Solam; Old, Lloyd J.; Arden, Karen C.

doi:10.1159/000134734

Cited by 88 publications

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“…Although nearly all of the hitherto known genes encoding CT antigens have been mapped to the X chromosome (41), mapping of the human KM-HN-1 gene has been assigned to chromosome 4. Furthermore, some CT antigens, e.g., MAGE, GAGE, and NY-ESO-1, were shown to be members of multigene families (42,43), but the family gene of KM-HN-1 was not found.…”

Section: Discussionmentioning

confidence: 99%

Identification of a Novel Human Cancer/Testis Antigen, KM-HN-1, Recognized by Cellular and Humoral Immune Responses

Monji

Nakatsura

Senju

et al. 2004

Clinical Cancer Research

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Purpose: We used serologic screening of a cDNA expression library of human testis to identify novel cancer/ testis antigens that elicit both humoral and cellular immune responses in cancer patients.Experimental Design and Results: We identified a novel gene designated KM-HN-1 the expression of which is testisspecific among normal tissues; it contains coiled coil domains and a leucine zipper motif and encodes a putative protein consisting of 833 amino acids. KM-HN-1 expression was observed in various cancer tissues and cancer cell lines at both mRNA and protein levels. Immunofluorescence staining of an esophageal cancer cell line revealed that KM-HN-1 protein was present exclusively in the nucleus during mitosis. Recombinant KM-HN-1 protein was produced, and used for ELISA to quantitate levels of IgG antibody specific to KM-HN-1. Higher levels of IgG antibodies specific to KM-HN-1 were detected in many types and numbers of cancer patients but not in healthy donors. The CTL lines specific to KM-HN-1, generated from HLA-A*2402-positive healthy donors and cancer patients, killed human leukocyte antigen (HLA)-A24-positive cancer cells expressing KM-HN-1 but not cell lines that did not express either KM-HN-1 or HLA-A24. Conclusions:We identified a novel cancer/testis antigen, KM-HN-1, which elicited humoral immune responses in patients with various types of cancer. Furthermore, KM-HN-1-specific CTLs could be generated from both healthy donors and cancer patients, which indicated that KM-HN-1 can be a candidate for an ideal target for cancer immunotherapy.

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Section: Discussionmentioning

confidence: 99%

Identification of a Novel Human Cancer/Testis Antigen, KM-HN-1, Recognized by Cellular and Humoral Immune Responses

Monji

Nakatsura

Senju

et al. 2004

Clinical Cancer Research

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“…1,2 The prototype examples of CT antigens are MAGE-A antigens and NY-ESO-1 antigen. MAGE-A antigens, including MAGE-A1 and MAGE-A3, are encoded by a multigene family on chromosome X and were the first human tumor antigens shown to elicit spontaneous cytotoxic T-cell response in cancer patients.…”

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confidence: 99%

“…3,4 NY-ESO-1, similarly encoded by a gene family on chromosome X, was also noted to have testis-restricted expression. 2 Compared with MAGE, however, NY-ESO-1 is significantly more immunogenic, often eliciting both humoral and cellular immune responses in patients with NY-ESO-1-positive malignancies. [5][6][7] In contrast to their limited expression in normal testicular germ cells, both MAGE and NY-ESO-1 have been shown to be aberrantly expressed in a proportion of various types of human cancers.…”

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confidence: 99%

Cancer/testis antigen CT45: Analysis of mRNA and protein expression in human cancer

Chen

Hsu

Lee

et al. 2009

Intl Journal of Cancer

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CT45 is a cancer/testis gene that we previously identified by massively parallel signature sequencing. Encoded by a multigene family on chromosome X, CT45 showed restricted mRNA expression to normal testis and various cancers. In this study, monoclonal antibodies were generated against recombinant CT45 protein, and CT45 protein expression in normal and tumor tissues was evaluated by immunohistochemical analysis. In adult normal tissue, CT45 expression was restricted to testicular germ cells, detected as a nuclear protein mainly at the stage of primary spermatocytes. In tumors, CT45 protein expression correlated with the mRNA levels detected by quantitative RT-PCR, and most lung cancer and ovarian cancers with CT45 mRNA at levels >1% of testicular expression were CT45 protein-positive. In positive cases, CT45 showed expression patterns that ranged from diffuse strong staining to heterogeneous and patchy expression. In lung cancer, CT45 expression was least frequent in adenocarcinoma, more frequent in squamous cell carcinoma and neuroendocrine tumors. Using tissue microarrays, 376 lung cancer, 219 ovarian cancer and 155 breast cancer were evaluated for CT45 protein expression. The expression frequency was highest in ovarian cancer (37%), followed by lung cancer (13%) and lowest in breast cancer (<5%). Given the focal nature of CT45 expression in many cases, these numbers represented the minimal frequency of expression in these tumor types. In summary, the expression frequency and characteristics of CT45 expression are similar to other CT cancer vaccine targets currently in clinical trials, e.g., NY-ESO-1 and MAGE-A, suggesting CT45 as a potentially useful cancer target. ' 2009 UICC

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“…In this case, NY-ESO-1 was found by using serum from a patient with squamous cell carcinoma (SCC) of the oesophagus. 1,2 Expression of NY-ESO-1 protein has been shown in multiple cancer types (Table 1), as well as in spermatogonia, oogonia and placenta. 3,4 Although NY-ESO-1 mRNA expression has been detected at low levels in some other normal tissues, it is unclear whether this is significant in the absence of detectable protein.…”

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confidence: 99%

Directions in the immune targeting of cancer: Lessons learned from the cancer‐testis Ag NY‐ESO‐1

et al. 2006

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Summary Since the early 1990s, numerous cancer Ag have been defined and for a handful of these there is now some clinical experience, which has made it possible to assess their value as targets for cancer immunotherapy. The cancer-testis Ag have been particularly attractive because their expression is limited to cancer and virtually no nonmalignant cells apart from germ cells and trophoblast. Among these, NY-ESO-1 has been the focus of our attention. The exceptional immunogenicity of this Ag coupled with its widespread distribution among many cancer types make it a very good vaccine candidate, with the potential to be used in vaccines against many types of malignancies. This article reviews emerging knowledge about the biology of NY-ESO-1 and experience with the early clinical development of vaccines directed against NY-ESO-1. These early studies have yielded a wealth of information about the immunology of NY-ESO-1 and set the scene for future clinical strategies for immune targeting of cancer.Key words: cancer immunology, cancer-testis Ag, cancer vaccine, dendritic cell, ISCOMATRIX, NY-ESO-1. Biology of NY-ESO-1NY-ESO-1 was first discovered using 'SERological identification of antigens by recombinant EXpression cloning' (SEREX). This is a method used for identifying the antibody repertoire of cancer-bearing patients by screening their serum against an expression library that typically displays protein Ag derived from a cancer source such as an autologous tumour or a cell line. In this case, NY-ESO-1 was found by using serum from a patient with squamous cell carcinoma (SCC) of the oesophagus. 1,2 Expression of NY-ESO-1 protein has been shown in multiple cancer types (Table 1), as well as in spermatogonia, oogonia and placenta. 3,4 Although NY-ESO-1 mRNA expression has been detected at low levels in some other normal tissues, it is unclear whether this is significant in the absence of detectable protein. 4,5 Other genes with similar names (NY-ESO-2, -3, -4, -5, -6, -7, -8) have no homology with NY-ESO-1. 2 The NY-ESO-1 gene is located on chromosome Xq28, 1 which carries a disproportionately high number of cancertestis (CT) Ag genes. 6 Up to 10% of the genes on chromosome X are CT Ag genes. The expression of these genes seems to be related to the demethylation of the promoter regions because experimental demethylation leads to the upregulation of CT Ag expression. [7][8][9][10][11][12][13][14][15][16][17][18] The NY-ESO-1 gene encodes a protein of 180 amino acids with M r 18 kDa, 2 which is expressed primarily in the cytoplasm although nuclear expression can be seen in some spermatogonia. 4 A homologue of NY-ESO-1, termed LAGE-1, was identified using representational difference analysis. 14 LAGE-1 and NY-ESO-1 are 84-89% homologous at the protein level. 14 Alternative splicing of LAGE-1 mRNA leads to the expression of two major transcripts encoding proteins of 210 and 180 amino acids, respectively. LAGE-1 is expressed in a wide variety of cancers (Table 1), usually, but not always, in conjunction with NY-ESO-1 or ...

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Genomic cloning and localization of CTAG, a gene encoding an autoimmunogenic cancer-testis antigen NY-ESO-1 to human chromosome Xq28

Cited by 88 publications

References 0 publications

Identification of a Novel Human Cancer/Testis Antigen, KM-HN-1, Recognized by Cellular and Humoral Immune Responses

Identification of a Novel Human Cancer/Testis Antigen, KM-HN-1, Recognized by Cellular and Humoral Immune Responses

Cancer/testis antigen CT45: Analysis of mRNA and protein expression in human cancer

Directions in the immune targeting of cancer: Lessons learned from the cancer‐testis Ag NY‐ESO‐1

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