Anti-MAGEA1 monoclonal antibody, clone TQN393

Cancer testis antigens (CTAs) are proteins that are normally expressed only in male germ cells and are aberrantly upregulated in a variety of cancers such as melanomas and lung cancer. MAGEA proteins belong to Class I CTAs and are being utilized as targets for cancer immunotherapy. Despite the discovery of the first CTA (MAGEA1) 20 years ago, the functions of these proteins remain poorly understood and evidence suggests both oncogenic as well as tumor suppressive roles for these proteins. Herein, we investigated the role of MAGEA4 in promoting cell growth. When overexpressed, MAGEA4 promotes growth of spontaneously transformed normal oral keratinocytes (NOK-SI). To understand the mechanism of growth stimulation by MAGEA4, we explored the effect of overexpressing MAGEA4 on cell cycle and apoptosis. MAGEA4 inhibits growth arrest of cells in the GI phase of the cell cycle. We also found that overexpression of MAGEA4 inhibits G418-induced apoptosis of NOK-SI cells. Interestingly, this inhibition was accompanied by repression of two p53 downstream genes, BAX and CDKNIA. Our results indicate that MAGEA4 promotes growth by preventing cell cycle arrest and by inhibiting apoptosis mediated by the p53 transcriptional targets.

ObjectivesAutoantibodies tumor-associated antigens (TAAs) could be a valuable tool for the diagnosis or early detection of cancer due to their relatively high specificity and stability. The purpose of this study is to detect the level of tumor-associated autoantibodies in lung cancer and assess the diagnostic potential of autoantibodies in screening strategy for early stage lung cancer. Materials and MethodsLevels of tumor-associated autoantibodies (AAbs) were measured against a panel of seven TAAs (p53, PGP9.5, SOX2, GAGE7, GBU4-5, CAGE and MAGEA1) in 397 patients with pulmonary lesions (305 with newly diagnosis of NSCLC, 47 with SCLC and 45 with benign nodule) and 74 control persons without any nodules in the lung after chest MDCT scan. The sensitivity, specificity for patients and control persons, positive rate of the panel in different pathology, stage, size of lesion, age and gender were compared and analyzed. ResultsThe AAbs panel could distinguish malignant lesions from benign lesions and control people, with sensitivity of 56.53% and specificity of 91.60%. The specificity could be further increased to 95.80%, when combined with CT. The AAbs also showed high diagnostic value of malignant nodule, and it would be a new method for judgment of malignant nodules that are less than 8 mm in diameter. No significant differences were seen based on pathology, NSCLC stages, tumor size, age or gender. ConclusionThis assay confirms the value of AAbs panel as a diagnostic tool combined with CT scan.