| With the development of biotechnology, increasing tumor antigens and their epitopes have been identified, which has been the foundation of tumor immunology and tumor vaccine. Of all these tumor antigens, cancer/testis antigen family has been the attractive one due to their tumor-specific expression and potent immunogenecity in inducing both CTL-mediated response and antibody-mediated response. Presently, the expression of cancer/testis antigens, including MAGE, GAGE, BAGE, NY-ESO-1, SSX, SCP-1, CT7 and CT10, has been detected in various histological tumors and often has been the target for immunotherapy. Previous studies have shown that several cancer/testis antigens, such as MAGE-1, MAGE-2, MAGE-3, MAGE-12 and NY-ESO-1 were expressed in non-small-cell lung carcinoma, and immunotherapy based on MAGE-3 and NY-ESO-1 have been tested in clinical trials. However, due to the discrepancy of cancer/testis antigen expression in different patient and heterogeneity of tumor cells from the same patient, a vaccine targeted to several antigens has been the strategy for boosting the immune response. Therefore, to find new cancer/testis antigen in lung carcinoma is of theoretical and applicable significance. TRAG-3 antigen encoded by Taxol resistant associated gene is a new tumor associate antigen, which was found in an ovarian carcinoma cell line resistant to Taxol (SKOVTR) by differential display. It is now regarded as a member of the cancer/testis antigen family, due to its specific expression by tumor cells but not normal tissues with the exception of testis, and its location on the X chromosome. Based on its expression model and high frequency in lung carcinoma cell lines, we proposed that TRAG-3 might be a target for immunotherapy in the treatment of lung carcinomas. On the other hand, approaches to vaccine-based immunotherapy of human cancer may ultimately require targets that are both tumour-specific and immunogenic. CTL recognize target cells through recognition to the antigen expressed by these cells, so TRAG-3 expression in lung carcinoma cells is the basic condition for TRAG-3 as a target for immunotherapy. Additionally, TRAG-3 must have the epitope that could elicit CTL response. These two criteria are necessary for TRAG-3 as a target for immunotherapy in the treatment of malignant tumor. However, it was found in the first part of our present research that 54% of non-small cell lung carcinomas could express TRAG-3, which expression level of TRAG-3 may be below the threshold for immune recognition. These data highlight the urgent need for the identification of novel compounds that could augment the immunogenecity of lung cancer cells. In addition, careful selection of the method of tumor vaccination is pivotal to assure the curative effect of immunotherapy. Therefore, an ideal modality would induce or enhance the expression of antigen, as well as to elicit a potent CTL response. Previous published data have shown that the expression of cancer/testis antigen, such as MAGE and NY-ESO-1 is due to demethylation of the genome. Therefore, scientists in this field proposed that re-expression of silenced cancer/testis antigen might be initiated through demethylation. The fact that demethylation agents, such as 5-Aza-2′-deoxyazacytidine could induce the expression of MAGE-1, MAGE-3 and NY-ESO-1 support this proposal. On the other hand, dendritic cell (DC)-based vaccine is the most intriguing of all tumor vaccines including: tumor-based vaccines, peptide-based vaccines, engineered vaccine and DNA vaccines. Clinical trials using a DC-based vaccination method have made great progress and showed tremendous therapeutic potential in the treatment of cancer.Based on the above-mentioned details, we want to explore TRAG-3 as a target for immunotherapy in the treatment of lung cancer and its possible use in clinic as following: (1) Detect the expression of TRAG-3 in non-small-cell lung carcinomas and explore its clinical significance; (2) Explore the possibility that 5-Aza-2′-deoxyazacytidine induce the expres...
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