Oncogenic activity and cellular functionality of melanoma associated antigen A3.

Cancer testis antigen Melanoma associated antigen A3 (MAGE-A3) has been subject of research for many years. Being expressed in various tumor types and influencing proliferation, metastasis, and tumor pathogenicity, MAGE-A3 is an attractive target for cancer therapy, particularly because in healthy tissues, MAGE-A3 is only expressed in testes and placenta. MAGE-A3 acts as a cellular master regulator by stimulating E3 ubiquitin ligase tripartite motif-containing protein 28 (TRIM28), resulting in regulation of various cellular targets. These include tumor suppressor protein p53 and cellular energy sensor AMP-activated protein kinase (AMPK). The restricted expression of MAGE-A3 in tumor cells makes MAGE-A3 an attractive target for vaccine-based immune therapy. However, although phase I and phase II clinical trials involving MAGE-A3-specific immunotherapeutic interventions were promising, large phase III studies failed. This article gives an overview about the role of MAGE-A3 as a cellular master switch and discusses approaches to improve MAGE-A3-based immunotherapies.