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Cancer-testis Antigens (cancer-testi + antigen)
Selected AbstractsJKT-1 is not a human seminoma cell lineINTERNATIONAL JOURNAL OF ANDROLOGY, Issue 4 2007Jeroen de Jong Summary The JKT-1 cell line has been used in multiple independent studies as a representative model of human testicular seminoma. However, no cell line for this specific tumour type has been independently confirmed previously; and therefore, the seminomatous origin of JKT-1 must be proven. The genetic constitution of the JKT-1 cells was determined using flow cytometry and spectral karyotyping, as well as array comparative genomic hybridization and fluorescent in situ hybridization. Marker profiling, predominantly based on differentially expressed proteins during normal germ cell development, was performed by immunohistochemistry and Western blot analyses. Moreover, genome wide affymetrix mRNA expression and profiling of 157 microRNAs was performed, and the status of genomic imprinting was determined. A germ cell origin of the JKT-1 cells was in line with genomic imprinting status and marker profile (including positive staining for several cancer-testis antigens). However, the supposed primary tumour, from which the cell line was derived, being indeed a classical seminoma, was molecularly proven not to be the origin of the cell line. The characteristic chromosomal anomalies of seminoma, e.g. gain of the short arm of chromosome 12, as well as the informative marker profile (positive staining for OCT3/4, NANOG, among others) were absent in the various JKT-1 cell lines investigated, irrespective of where the cells were cultured. All results indicate that the JKT-1 cell line is not representative of human seminoma. Although it can originate from an early germ cell, a non-germ cell derivation cannot be excluded. [source] MAGE-A9 mRNA and protein expression in bladder cancerINTERNATIONAL JOURNAL OF CANCER, Issue 10 2007Valérie Picard Abstract In a previous analysis, we showed that MAGE-As were the most frequently expressed cancer-testis antigens in human bladder tumours. Here, we further characterized by RT-PCR the expression of this family of genes by analyzing specifically MAGE-A3, -A4, -A8 and -A9 mRNAs in 46 bladder tumours and 10 normal urothelia. We found that they were expressed in 30, 33, 56 and 54% of tumours, respectively. Although MAGE-A8 was the most frequent, its expression was low and was also found in most normal urothelia. The other MAGE-A mRNAs were all tumour-specific but MAGE-A9 mRNA was expressed at a higher level and was two times more frequent in superficial than in invasive tumours. To study the expression of the protein, we produced 2 MAGE-A9-specific monoclonal antibodies (mAbs) presenting no cross-reactivity with other MAGE-A proteins. MAb 14A11, was used to analyse the expression of the antigen in testis and tumour samples by immunohistochemistry. In testis, MAGE-A9 expression was restricted to primary spermatocytes. Most bladder tumours that expressed the MAGE-A9 transcript were positive with mAb 14A11. Staining was heterogeneous but half of the tumours showed over 75% positive cells. Finally, we showed that treatment of bladder cancer cells with the methylation inhibitor, 5-aza-2,-deoxycytidine, alone or in combination with the histone deacetylase inhibitors MS-275 and 4-phenylbutyrate could strongly induce the expression of MAGE-A9. These results show that MAGE-A9 is frequently expressed in superficial bladder cancer and could be a relevant target for immunotherapy or chemoimmunotherapy because its expression can be induced by chemotherapeutic drugs. © 2007 Wiley-Liss, Inc. [source] Cancer vaccines: Where are we going?ASIA-PACIFIC JOURNAL OF CLINICAL ONCOLOGY, Issue 2010Jonathan CEBON Abstract The discovery that the immune system can distinguish molecular targets on cancer cells has led to efforts to develop cancer immunotherapeutics that can improve the recognition and effective elimination of tumor cells. Several types of tumor antigens are recognized by T lymphocytes, which are classified according to patterns of gene expression or protein distribution. Of particular interest is the group of molecules known as cancer-germline or cancer-testis antigens. As the relationship between the immune system and cancer has become clearer, so too have the challenges in designing effective cancer immunotherapeutics: (i) antigens need to be specifically selected based on ideal characteristics, such as tissue distribution that is restricted to tumors; (ii) selected antigens need to be combined with adjuvant agents that enhance their immunogenicity and yield robust responses; (iii) vaccination should be timed to pre-empt the development of regulatory suppressive immune mechanisms; and (iv) if suppressive regulatory mechanisms do arise, specific antagonists may be needed to enhance pro-immune outcomes. These challenges are shaping current and future research in this area. [source] Seroreactivity against MAGE-A and LAGE-1 proteins in melanoma patientsBRITISH JOURNAL OF DERMATOLOGY, Issue 2 2003D. Usener Summary Background Cancer-testis antigens exemplify a growing number of tumour antigens which are expressed in a variety of malignancies, but not in normal tissues other than germ cells, primarily those of the testis. Objectives To investigate the humoral response to known cancer-testis antigens in melanoma patients. Methods We used phage clones coding for seven different melanoma antigens MAGE-A or LAGE-1A proteins. These clones were isolated using the newly developed DNA hybridization analysis of recombinantly expressed cDNA libraries (HYREX) approach. HYREX combines the advantage of a nonradioactive library screening method with the possibility of subsequently analysing the serological response to the recombinant proteins. We isolated clones coding for MAGE-A1, -A3, -A4b, -A6, -A9 and -A12, as well as LAGE-1A. Additionally, we correlated gene expression and seroreactivity. Results Between 13% and 27% of sera (n = 15) were reactive against individual tumour antigens. We found the presence of specific antibodies was, with only two exceptions, generally correlated with mRNA expression of the antigen within cell lines derived from the same patient. While cross-reactivity of patients' IgG might play a role in these cases, antibodies from patients' sera were able to distinguish even the closely related MAGE-A3 and -A6. In general, the mRNA expression frequency was higher than the detected IgG responses. Conclusions Antibody recognition of specific tumour antigens by patients' sera may be used for evaluating the possible immunogenicity of new antigens; serological tests could be used for tumour monitoring purposes. [source] | ||||||||||