MAGE-A antigens as targets for cancer immunotherapy.

Targeted anti-cancer therapies aim at reducing side effects while retaining their anti-cancer efficacy. Immunotherapies e.g. monoclonal antibodies, adoptive T cell therapy and cancer vaccines are used to combat cancer, but the number of available cancer specific targets is limited and new approaches are needed to generate more effective and patient tailored treatments. Unique cancer intracellular epitopes can be presented on the cell surface by MHC class I molecules, which can function as epitopes for targeted therapies. The intracellular MAGE proteins belong to a sub-class of Cancer Testis (CT) antigens which are expressed in germline cells and a wide variety of tumors of different histological origin. Evidence has emerged that their expression is linked to pro-tumorigenic activities like increased cell motility, resisting cell death, and tumor promoting inflammation. Intracellular MAGE proteins are processed by the proteasome and their peptides are presented by MHC class I molecules on the cell surface of cancer cells thereby making them ideal cancer specific antigens. Here we review the previous and ongoing (pre-) clinical studies on the use of surface expressed MAGE antigens for their employment in targeted anti-cancer therapies. We present and analyze study outcomes and discuss possible future directions and improvements for MAGE directed anti-cancer immunotherapies.