Anti-MAGEA4 monoclonal antibody, clone 2G0

Background. Cancer testis antigens (CTAs) are T-cell-defined tumor-associated antigens encoded by the genes and gene families such as MAGE, NY-ESO-1, and others. Their expression in a wide variety of malignant neoplasms but absence in all normal adult tissue except testicular germ cells makes them attractive targets for immunotherapy of cancer, Primary mucosal melanomas of the head and neck (HNMM) are rare aggressive malignant tumors that are usually difficult to treat. CTAs may provide useful targets for therapy; however, their expression in HNMM is not known. Methods. We analyzed 40 initial, 15 recurrent, and 15 metastatic HNMM to nonmucosal locations from 64 patients (oral, n = 30; sinonasal, n = 34). Immunohistochemistry was performed on archival tissue with monoclonal antibodies 5713, CT7-33, and ES121 to the following CTAs: MAGE-A4, CT7 (MAGE-Cl), and NY-ESO-1, respectively. Results. CT7, MAGE-A4, and NY-ESO-1 expression was seen in 73%, 61%, and 24% of tumors, respectively, with 81% of the tumors expressing at least one of the CTAs. CT7 and MAGE-A4 were significantly more frequently expressed in tumors composed of epithelioid cells than spindle cells (p = .05). CTA expression did not correlate with disease progression, overall survival, and disease-specific survival. Conclusions. CT7, MAGEA4, and NY-ESO-1 are frequently expressed in HNMM and may be potential targets for CTA-based immunotherapy. The expression does not seem to have prognostic significance. (C) 2004 Wiley Periodicals, Inc.

Background: Cancer/testis (CT) genes are expressed only in the germ line and certain tumors and are most frequently located on the X-chromosome (the CT-X genes). Amongst the best studied CT-X genes are those encoding several MAGE protein families. The function of MAGE proteins is not well understood, but several have been shown to potentially influence the tumorigenic phenotype. Methodology/Principal Findings: We undertook a mutational analysis of coding regions of four CT-X MAGE genes, MAGEA1, MAGEA4, MAGEC1, MAGEC2 and the ubiquitously expressed MAGEE1 in human melanoma samples. We first examined cell lines established from tumors and matching blood samples from 27 melanoma patients. We found that melanoma cell lines from 37% of patients contained at least one mutated MAGE gene. The frequency of mutations in the coding regions of individual MAGE genes varied from 3.7% for MAGEA1 and MAGEA4 to 14.8% for MAGEC2. We also examined 111 fresh melanoma samples collected from 86 patients. In this case, samples from 32% of the patients exhibited mutations in one or more MAGE genes with the frequency of mutations in individual MAGE genes ranging from 6% in MAGEA1 to 16% in MAGEC1. Significance: These results demonstrate for the first time that the MAGE gene family is frequently mutated in melanoma.