A nonapeptide encoded by human gene MAGE-1 is recognized on HLA-A1 by cytolytic T lymphocytes directed against tumor antigen MZ2-E.

Abstract

SummaryWe have reported the identification of human gene MAGE-1, which directs the expression of an antigen recognized on a melanoma by autologous cytolytic T lymphocytes (CTL). We show here that CTL directed against this antigen, which was named MZ2-E, recognize a nonapeptide encoded by the third exon of gene MAGE-1 . The CTL also recognize this peptide when it is presented by mouse cells transfected with an HLA-A1 gene, confirming the association of antigen MZ2-E with the HLAA1 molecule. Other members of the MAGE gene family do not code for the same peptide, suggesting that only MAGE-1 produces the antigen recognized by the anti-MZ2-E CTL . Our results open the possibility of immunizing HLAA1 patients whose tumor expresses MAGE-1 either with the antigenic peptide or with autologous antigen-presenting cells pulsed with the peptide .

MAGE, BAGE and GAGE: tumour antigen expression in benign and malignant ovarian tissue

“…It is known that MAGE-1 and -3 are targets for specific immunotherapy as they encode peptide antigens that are presented in association with HLA class 1 molecules and are recognized by CTL. 'MAGE-I is expressed in association with HLA-AI and -CW 1601 (Traversari et al 1992; Van der Bruggen et al, 1994a), whereas MAGE-3 is expressed in association with HLA-A I and HLA-A2.01 (Gaugler et al, 1994;Van der Bruggen et al, 1994b). Pilot studies have commenced to assess the value of MAGE-1-A 1, MAGE-3-A I and MAGE-3-A2 peptides as tumour vaccines in a number of tumour types -including malignant melanoma -that have previously been shown to express the MAGE genes.…”

An optimum anti-melanoma response in mice immunized with fibroblasts transfected with DNA from mouse melanoma cells requires the expression of both syngeneic and allogeneic MHC-determinants

“…The products of genes that specify TAAs expressed by melanoma cells, such as BAGE, GAGE-1, MAGE-1, MAGE-2, MAGE-3, gp100 and tyrosinase, among others, have been identified as the targets of CTLs. [5][6][7][8][9][10][11][12][13] It is likely that these TAAs are only several representations of an undefined, and possibly large number of TAAs expressed by different cells that comprise the malignant cell population. Genetic instability is a characteristic phenotype of cancer cells.…”

Adenovirus-mediated expression of melanoma antigen gp75 as immunotherapy for metastatic melanoma

“…1,2 Specific antigens identified in murine and human melanomas include MAGE-1 and MAGE-3, MART 1/melan-A, tyrosinase, gp100, mutated CDK4, a 97 kDa cell surface glycoprotein melanotransferrin, a 66 kDa protein and a 75 kDa tyrosinase-related protein-1 (gp75). [3][4][5][6][7][8][9][10][11][12][13][14] Based on extensive data in murine models and in human cancers showing that the immune system can recognize antigens expressed by melanoma, therapeutic strategies have been designed to augment immune recognition of melanoma antigens utilizing attenuated tumor cells or cell lysates, either alone or mixed with immune adjuvants, tumor cells genetically modified to express cytokines, specific antigenic peptides, or gene transfer vaccination approaches using cDNAs coding for specific antigens. Gp75 is one of the melanoma antigens that has been evaluated in protein-based vaccine strategies.…”