MAGE-A antigens as targets in tumour therapy
ABSTRACT MAGE-A proteins constitute a sub-family of Cancer-Testis Antigens which are expressed mainly, but not exclusively, in germ cells. They are also expressed in various human cancers where they are associated with, and may drive, malignancy. MAGE-A proteins are highly immunogenic and are considered as potential targets for cancer vaccines and/or immuno-therapy. Moreover, recent advances in our understanding of their molecular pathology have revealed interactions that offer potential as therapeutic targets. Here we review recent progress in this area and consider how these interactions might be exploited, especially for the treatment of malignant cancers for which available treatments are inadequate.
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- "MAGE - A and their epitope peptides constitute important targets for anti - tumour immunotherapy . Their strict expression on the surface of malignant cells has led to several immuno - therapeutic trials targeting some of these members ( Sang et al , 2011 ; Meek and Marcar , 2012 ) . Thus , the detection of the elevated levels of MAGE - A1 , - A2 and - A3 in the blood of breast cancer patients could become a blood - based tool for early cancer diagnosis and a potential predictive biomarker for MAGE - directed immu - notherapies . "
ABSTRACT: Background:MAGE-A (melanoma-associated antigen-A) are promising targets for specific immunotherapy and their expression may be induced by the epigenetic factor BORIS.Methods:To determine their relevance for breast cancer, we quantified the levels of MAGE-A1, -A2, -A3, -A12 and BORIS mRNA, as well as microRNAs let-7b and miR-202 in pre- and postoperative serum of 102 and 34 breast cancer patients, respectively, and in serum of 26 patients with benign breast diseases and 37 healthy women by real-time PCR. The mean follow-up time of the cancer patients was 6.2 years.Results:The serum levels of MAGE-A and BORIS mRNA, as well as let-7b were significantly higher in patients with invasive carcinomas than in patients with benign breast diseases or healthy women (P<0.001), whereas the levels of miR-202 were elevated in both patient cohorts (P<0.001). In uni- and multivariate analyses, high levels of miR-202 significantly correlated with poor overall survival (P=0.0001). Transfection of breast cancer cells with synthetic microRNAs and their inhibitors showed that let-7b and miR-202 did not affect the protein expression of MAGE-A1.Conclusions:Based on their cancer-specific increase in breast cancer patients, circulating MAGE-A and BORIS mRNAs may be further explored for early detection of breast cancer and monitoring of MAGE-directed immunotherapies. Moreover, serum miR-202 is associated with prognosis.British Journal of Cancer advance online publication, 1 July 2014; doi:10.1038/bjc.2014.360 www.bjcancer.com.British Journal of Cancer 07/2014; 111(5). DOI:10.1038/bjc.2014.360 · 4.82 Impact Factor
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ABSTRACT: Lung cancer has traditionally been considered relatively resistant to immunotherapies. However, recent advances in the understanding of tumor-associated antigens, anti-tumor immune responses, and tumor immunosuppression mechanisms have resulted in a number of promising immunomodulatory therapies such as vaccines and checkpoint inhibitors. Locally advanced non-small cell lung cancer is an optimal setting for these treatments because standard therapies such as surgery, radiation, and chemotherapy may enhance anti-tumor immune effects by debulking the tumor, increasing tumor antigen presentation, and promoting T-cell response and trafficking. Clinical trials incorporating immunomodulatory agents into combined modality therapy of locally advanced non-small cell lung cancer have shown promising results. Future challenges include identifying biomarkers to predict those patients most likely to benefit from this approach, radiographic assessment of treatment effects, the timing and dosing of combined modality treatment including immunotherapies, and avoidance of potentially overlapping toxicities.The Cancer Journal 01/2013; 19(3):247-262. DOI:10.1097/PPO.0b013e318292e51a · 3.61 Impact Factor
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ABSTRACT: Prevention of cancer remains the most promising strategy for reducing both its incidence and the mortality due to this disease. For more than four decades, findings from epidemiology, basic research and clinical trials have informed the development of lifestyle and medical approaches to cancer prevention. These include selective oestrogen receptor modulators and aromatase inhibitors for breast cancer, the 5-α-reductase inhibitors finasteride and dutasteride for prostate cancer, and the development of vaccines for viruses that are associated with specific cancers. Future directions include genetic, proteomic and other molecular approaches for identifying pathways that are associated with cancer initiation and development, as well as refining the search for immunologically modifiable causes of cancer.Nature Reviews Cancer 11/2012; 12(12). DOI:10.1038/nrc3397 · 29.54 Impact Factor