Melanoma or not? Cancer testis antigens may help

Lüftl, Matthias; Schüler, G; Jungbluth, Achim A.

doi:10.1111/j.1365-2133.2004.06260.x

Cited by 35 publications

(23 citation statements)

References 25 publications

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“…For this purpose, it is essential to determine the types of cancer that express CT antigens, at what frequency, and the pattern of expression within a given tumour, including percentage of positive cells, expression levels and the subcellular localization of expression. The expression of GAGE proteins in tumours has been addressed by RT -PCR in numerous studies, but until recently no anti-GAGE antibodies were available (Luftl et al, 2004;Akcakanat et al, 2006). In this study, we have generated a panel of GAGEreactive mAbs and used these to characterize the extent of heterogeneity in GAGE expression in malignancies.…”

Section: Discussionmentioning

confidence: 99%

“…This antibody, which recognized a 26-kDa band, similar to our anti-GAGE mAbs, was recommended only for Western blot applications by the manufacturer, but two recent studies have shown that this mAb is also suitable for immunohistochemical analysis (Luftl et al, 2004;Akcakanat et al, 2006). To compare the reactivity of this antibody with the reactivity of mAbs M2, M3 and M4, the anti-GAGE-7mAb was tested in parallel with M3 for reactivity with the panel of normal and cancer tissues by immunohistochemistry.…”

Section: Comparison Of the Reactivity Of The Anti-gage Mabs With Thatmentioning

confidence: 99%

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Restriction of GAGE protein expression to subpopulations of cancer cells is independent of genotype and may limit the use of GAGE proteins as targets for cancer immunotherapy

et al. 2006

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The GAGE cancer testis antigen gene family encodes products that can be recognized by autologous T cells, and GAGE proteins have been suggested as potential targets for cancer immunotherapy. Analysis of GAGE expression in tumours has primarily been performed at the level of gene transcription, whereas little is known about GAGE expression at the protein level. To evaluate the potential of GAGE proteins as targets for cancer-specific immunotherapy, we studied the expression of these proteins in normal and malignant cells/tissues using a novel panel of monoclonal antibodies. Immunohistochemical analysis of more than 250 cancer specimens demonstrated that GAGE proteins were frequently expressed in numerous cancer types and correlated with the expression of the cancer testis antigens MAGE-A1 and NY-ESO-1. Significant intercellular and subcellular differences in GAGE protein levels were observed, and most GAGE-positive tumours also contained cancer cells lacking GAGE expression. Studies of genetically homogenous cell lines with similar intercellular heterogeneous GAGE expression showed that GAGE expression was not associated with a specific genotype, but defined a phenotypically distinct population of cells. Surprisingly, in normal tissues we found that GAGE proteins were not restricted to testis, but were also present in a subset of oocytes of resting primordial follicles and in maturing oocytes. This is the first time that a cancer testis antigen has been reported in postfoetal oocytes. The lack of GAGE expression in a subset of cancer cells within GAGE-positive tumours has decisive implications for the development of GAGE-targeted cancer therapy.

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Section: Discussionmentioning

confidence: 99%

Section: Comparison Of the Reactivity Of The Anti-gage Mabs With Thatmentioning

confidence: 99%

Restriction of GAGE protein expression to subpopulations of cancer cells is independent of genotype and may limit the use of GAGE proteins as targets for cancer immunotherapy

et al. 2006

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“…This finding was in sharp contrast to the expression pattern of CD30 in virus-induced Hodgkin-like lymphadenopathies. mAb specific to cancer/testis antigens have been used to improve the diagnosis of various malignant tumors (1,36). The diagnosis of Hodgkin's lymphoma may be difficult for a variety of reasons.…”

Section: Discussionmentioning

confidence: 99%

Characterization and Expression of CT45 in Hodgkin's Lymphoma

Heidebrecht¹,

Claviez²,

Kruse³

et al. 2006

Clinical Cancer Research

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Purpose: The monoclonal antibody Ki-A10 (IgG1) generated after immunization of mice with Hodgkin's lymphoma cell line L428 detects a nuclear antigen in human tissues with a restricted distribution pattern similar to cancer/testis antigens.The aim of this study was to characterize the antigen and to determine the expression profile in Hodgkin's lymphoma. Experimental Design: The half-life and phosphorylation of the antigen were determined by radiolabeling. The antigen was characterized by immunopurification and sequencing. Demethylation of genes is used to induce cancer/testis antigens. Ki-A10-negative cells were treated with 5-aza-2 ¶-deoxycytidine. The Ki-A10 expression in paraffin-embedded tumors was determined immunohistochemically. Results: Immunopurification of the 25/22-kDa antigen and sequencing revealed a peptide of 14 amino acids corresponding to the gene product of the newly described gene family MGC27005, located on chromosome Xq26.3, now termed CT45. CT45 is significantly phosphorylated and down-regulated during mitosis. Demethylation of CT45-negative HeLa cells and stimulated peripheral blood lymphocytes induced CT45 expression. Except testis, immunohistochemical stainings of normal tissues, reactive lymphoid lesions, and most malignant tumors were negative. In comparison, 54 of 99 (55%) samples from pediatric and adolescent Hodgkin's lymphoma patients enrolled in the multicenter trial HD-95 stained Ki-A10 positive. Ki-A10 expression correlated with histologic subtypes (nodular sclerosis Hodgkin's lymphoma 68% versus mixed cellularity Hodgkin's lymphoma 40% versus nodular lymphocyte predominant Hodgkin's lymphoma 9%; P < 0.001).Conclusions: Ki-A10 is the first monoclonal antibody that detects CT45. As benign lymphoid lesions did not express CT45, the use of Ki-A10 antibody will facilitate the discrimination of Hodgkin's lymphoma from reactive lymphadenopathies.

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“…Discussion CT antigens, due to their tumor-associated expression pattern, have been widely studied as potential targets for immunotherapy (5) and markers for tumor diagnosis (32,33), e.g., in melanoma. On the protein level, the expression of CT antigens is restricted to malignant cells and germ cells, which does not pose an obstacle to an immunotherapeutic approach, because germ cells express low levels of HLA molecules and therefore cannot be recognized by vaccine-induced T-cell responses.…”

Section: Ct7-specific Cd4 + T-cell Clones Recognize Naturally Processmentioning

confidence: 99%

Fine analysis of spontaneous MAGE-C1/CT7–specific immunity in melanoma patients

Nuber

Curioni-Fontecedro

Matter

et al. 2010

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

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Cancer/testis (CT) antigens represent prime candidates for immunotherapy in cancer patients, because their expression is restricted to cancer cells and germ cells of the testis. MAGE-C1/CT7 is a CT antigen that is highly expressed in several types of cancers. Spontaneous occurrence of CT7-specific antibodies was previously detected by SEREX screen in a melanoma patient. However, naturally occurring CT7-specific T-cell responses have thus far not been detected. Peripheral blood mononuclear cells (PBMCs) from 26 metastatic melanoma patients expressing CT7 in their tumor lesions (CT7 + ) were analyzed for CT7-specific T-cell responses using overlapping peptides. CT7-specific CD4 + T-cell responses were detected in three patients (11.5%). These CT7-specific CD4 + T-cell responses were detectable in melanoma patients' PBMCs exclusively from preexisting CD45RA − memory CD4 + T-cell pool. Additional CT7-specific memory CD4 + T-cell responses were detected in CT7 + melanoma patients after depletion of CD4 + CD25high Treg cells showing that Treg cells impact on CT7-specific CD4 + T cells in melanoma patients. CT7-specific CD4 + T-cell clones were generated and used to define minimal epitopes, restriction elements, and confirm the recognition of naturally processed antigen. Surprisingly, these clones were able to secrete perforin and exert cytotoxicity. This study shows that CT7 can induce specific cellular immunity in melanoma patients. Based on these findings, CT7 will be further explored as a potential vaccine for melanoma immunotherapy.cancer/testis antigens | T-cell response

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Melanoma or not? Cancer testis antigens may help

Abstract: CTAs may be useful in the determination of suspected malignancy in cutaneous melanomas. The low incidence of particular CTAs can be overcome by increasing the number of CTAs analysed.

Cited by 35 publications

References 25 publications

Restriction of GAGE protein expression to subpopulations of cancer cells is independent of genotype and may limit the use of GAGE proteins as targets for cancer immunotherapy

Restriction of GAGE protein expression to subpopulations of cancer cells is independent of genotype and may limit the use of GAGE proteins as targets for cancer immunotherapy

Characterization and Expression of CT45 in Hodgkin's Lymphoma

Fine analysis of spontaneous MAGE-C1/CT7–specific immunity in melanoma patients

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