Antigens encoded by MAGE genes PD-L1
Antigens encoded by MAGE genes are of particular interest for cancer immunotherapy because of their strict tumoral specificity and because they are shared by many tumors.
MAGE-type genes are expressed by many tumors of different histological types and not by normal cells, except for male germline cells. Therefore, the antigens encoded by MAGE-type genes are strictly tumor specific and common to many tumors. Among the MAGE genes, MAGE-3 is one of the most frequently expressed in tumors. For instance, it is expressed in 76% of metastatic melanomas.
MAGE-A4 belongs to the family of genes that are specifically expressed in a variety of tumors. MAGE-A4-derived peptides are presented by MHC molecules at the cell surface to cytotoxic T-lymphocytes. Because the HLA-A*0201:MAGE-A4 complex occurs only on tumor cells, it is considered to be an appropriate target for immunotherapy.
MAGE-A1 tumor antigen can fully activate the mouse peptide-specific CTL lines to produce IFN-gamma. Tumor-specific shared antigens, such as those of the MAGE gene family, are expressed by tumors of different histological types.
Programed cell death protein 1 (PD-1)
is a cell surface receptor. PD-1 and its ligand PD-L1 are crucial immune checkpoints to downregulate T cell activation, tolerance and immunopathology. Several types of cancer cells overexpress PD-L1 in order to escape from the PD-1/PD-L1 immunosurveillance mechanism. Human PD-L1 inhibitors
are peptide-based molecules. They bind to human PD-1 and inhibit PD-1/PD-L1 binding. These peptides have anchor residues that influence binding of hPD-L1 to hPD-1. Developing inhibitors specifically blocking the PD-1/PD-L1 pathway has become a popular approach toward cancer treatment.