NY-ESO-1 and CTp11 Expression May Correlate with Stage of Progression in Melanoma

Goydos, James S.; Patel, Mitesh; Shih, Weichung Joe

doi:10.1006/jsre.2001.6148

Cited by 57 publications

(33 citation statements)

References 43 publications

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“…This antigen is preferentially expressed in moderately and poorly differentiated HCC. Similar results were also shown in NY-ESO-1 expression in melanoma 28 and MAGE-A4 in transitional cell carcinoma. 29 Second, the IHC staining pattern is heterogeneous in different HCC samples, the expression of the FATE/BJ-HCC-2 antigen in tumor cells ranging from focal to a large mass of tumor cells.…”

Section: Discussionsupporting

confidence: 85%

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: Discussionsupporting

confidence: 85%

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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“…However, the study consisted of fewer cases, and tumor and metastatic lesion were not derived from the same patients (39). Likewise, few studies have looked at patterns of NY-ESO-1 expression in melanoma, although one smaller study did find NY-ESO-1 mRNA expression to be increased in metastases compared with primary samples (32). Two other studies found NY-ESO-1 expression in f36% (23) and 31.6% of melanomas (40), respectively.…”

Section: Discussionmentioning

confidence: 99%

Tumor Antigen Expression in Melanoma Varies According to Antigen and Stage

Barrow

Browning

MacGregor

et al. 2006

Clinical Cancer Research

215

194

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Purpose: Melanoma cells express antigens that can induce T-cell and antibody responses.Obtaining a detailed understanding of antigen expression in primary and metastatic melanoma is essential if these molecules are to be useful targets for immunotherapy of melanoma. Experimental Design: Malignant melanomas (n = 586) from 426 patients were typed for antigen expression. Multiple samples were available from 86 individuals, enabling analysis of antigen expression patterns over time. Paraffin-embedded samples were tested by immunohistochemistry for the presence of the differentiation antigens: gp100, Melan-A, tyrosinase, and the ''cancer/testis'' antigens MAGE-A1, MAGE-A4, and NY-ESO-1. Results: Samples were primary tumors (n = 251), lymph node metastases (n = 174), s.c. metastases (n = 71), and distant metastases (n = 90). The differentiation antigens were strongly expressed in 93% to 95% of tumors regardless of stage. In contrast, the frequency of cancer/ testis antigen expression in primary tumors for MAGE-A1, MAGE-A4, and NY-ESO-1 was lower (20%, 9%, and 45%, respectively). MAGE-A1 and MAGE-A4 were acquired with advancing disease (to 51% and 44% in distant metastases, respectively) but not NY-ESO-1, which remained positive in 45%. MAGE-A1 expression was twice as prevalent in ulcerated primaries as in nonulcerated primaries (30% versus 15%; P = 0.006) and in thicker as opposed to thin melanomas (26% versus 10%; P = 0.1). Conclusions: This large series describes patterns of antigen expression in melanoma and their evolution over time. This will help inform decisions about selection of patients and target antigens for melanoma immunotherapy clinical trials.

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“…54 As a cancer that expresses NY-ESO-1 grows and progresses, spontaneous anti-NY-ESO-1 immune responses are seen more frequently and often correlate broadly with the burden of disease. 36 …”

Section: Immunogenicity and Tolerancementioning

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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NY-ESO-1 and CTp11 Expression May Correlate with Stage of Progression in Melanoma

Cited by 57 publications

References 43 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

Tumor Antigen Expression in Melanoma Varies According to Antigen and Stage

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

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